Showing papers on "Cell growth published in 1978"
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TL;DR: Cell shape was found to be tightly coupled to DNA synthesis and growth in nontransformed cells, suggesting a mechanism that is important in growth control of mammalian cells, and providing a more fundamental interpretation of such phenomena as density dependent inhibition of cell growth and anchorage dependence.
Abstract: Tissue culture plastic adhesivity was precisely varied by applying different concentrations of poly(2-hydroxyethyl methacrylate). The extent of cell spreading was thus accurately controlled so that cells cultured on these substrata could be held at any one of a graded series of quantitated cell shapes. Cell shape was found to be tightly coupled to DNA synthesis and growth in nontransformed cells. These findings suggest a mechanism that is important in growth control of mammalian cells, and provide a more fundamental interpretation of such phenomena as density dependent inhibition of cell growth and anchorage dependence.
2,406 citations
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TL;DR: It is likely that PDGF is released from platelets at sites of vascular damage and that it contributes toward the cell proliferation and connective tissue formation seen in healing wounds and in arteriosclerotic lesions.
659 citations
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TL;DR: Eukaryote DNA can be divided into genic DNA, which codes for proteins (or serves as recognition sites for proteins involved in transcription, replication and recombination), and nucleoskeletal DNA (S-DNA), which exists only because of its nucleoskeleton role in determining the nuclear volume.
Abstract: The 40,000-fold variation in eukaryote haploid DNA content is unrelated to organismic complexity or to the numbers of protein-coding genes. In eukaryote microorganisms, as well as in animals and plants, DNA content is strongly correlated with cell volume and nuclear volume, and with cell cycle length and minimum generation time. These correlations are simply explained by postulating that DNA has 2 major functions unrelated to its protein-coding capacity: (1) the control of cell volume by the number of replicon origins, and (2) the determination of nuclear volume by the overall bulk of the DNA: cell growth rates are determined by the cell volume and by the area of the nuclear envelope available for nucleocytoplasmic transport of RNA, which in turn depends on the nuclear volume and therefore on the DNA content. During evolution nuclear volume, and therefore DNA content, has to be adjusted to the cell volume to allow reasonable growth rates. The great diversity of cell volumes and growth rates, and therefore of DNA contents, among eukaryotes results from a varying balance in different species between r-selection, which favours small cells and rapid growth rates and therefore low DNA C-values, and K-selection which favours large cells and slow growth rates and therefore high DNA C-values. In multicellular organisms cell size needs to vary in different tissues: size differences between somatic cells result from polyteny, endopolyploidy, or the synthesis of nucleoskeletal RNA. Conflict between the need for large ova and small somatic cells explains why lampbrush chromosomes, nurse cells, chromatin diminution and chromosome elimination evolved. Similar evolutionary considerations clarify the nature of polygenes, the significance of the distribution of haploidy, diploidy and dikaryosis in life cycles and of double fertilization in angiosperms, and of heteroploidy despite DNA constancy in cultured cells, and other puzzles in eukaryote chromosome biology. Eukaryote DNA can be divided into genic DNA (G-DNA), which codes for proteins (or serves as recognition sites for proteins involved in transcription, replication and recombination), and nucleoskeletal DNA (S-DNA) which exists only because of its nucleoskeletal role in determining the nuclear volume (which it shares with G-DNA, and performs not only directly, but also indirectly by coding for nucleoskeletal RNA). Mechanistic and evolutionary implications of this are discussed.
646 citations
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TL;DR: A cell system has been developed to determine and dissect the controls that regulate normal myeloids cell growth, differentiation and malignancy, and to suggest a novel approach to the therapy of myeloid leukaemia.
Abstract: A cell system has been developed to determine and dissect the controls that regulate normal myeloid cell growth, differentiation and malignancy, and to suggest a novel approach to the therapy of myeloid leukaemia.
581 citations
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TL;DR: Four agents known to increase the level of cellular cAMP by different means increase the growth of colonies of cultured human epidermal cells and of keratinocytes derived from other stratified squamous epithelia, suggesting that cell proliferation in the intact epidermis is regulated through agents affecting cAMP.
457 citations
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TL;DR: It is reported that membranes may be prepared from A-431 cells that retain the ability to bind 125I-labelled EGF in a specific manner, and the binding of EGF to these membranes in vitro results in a marked stimulation of the phosphorylation of endogenous proteins in the presence of [γ-32P]ATP.
Abstract: EPIDERMAL GROWTH FACTOR (EGF) forms a complex with plasma membrane receptors in intact cells that initiates a series of biochemical events resulting in increased cell growth in vivo and in vitro1. The interaction of EGF with membrane receptors has been demonstrated in crude membrane preparations2, but no biochemical alteration of the membrane resulting from hormone binding has been detected. To clarify the molecular mechanisms regulating cell proliferation, specific biochemical reactions initiated by mitogens such as EGF need to be investigated in cell-free systems. As the human epidermoid carcinoma cell line A-431 has an extraordinarily high concentration of EGF receptors3,4 (2–3 x 106 receptors per cell), we have used a crude membrane preparation from these cells to look for an EGF-dependent alteration of membrane structure and/or function. We report here that (1) membranes may be prepared from A-431 cells that retain the ability to bind 125I-labelled EGF in a specific manner, and (2) the binding of EGF to these membranes in vitro results in a marked stimulation of the phosphorylation of endogenous proteins in the presence of [γ-32P]ATP.
420 citations
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TL;DR: A new approach to the sequential analysis of carcinogenesis in vivo is developed that delineates the first few steps in the process and is a quantitative assay for initiation of liver cancer, to investigate whether cell replication exerts its first effect on initiation or on some later step in the carcinogenic process.
Abstract: CELL proliferation has often been implicated in the development of cancer with chemicals1–3. Supportive evidence for this is the observation that several carcinogens that normally do not induce liver cancer in intact adult animals, especially with a single dose, become carcinogenic if administered as a single injection after partial hepatectomy (PH)1. In these conditions, it is thought that PH may act during initiation, presumably by fixation of some carcinogen-induced DNA damage through replication of the altered DNA. However, because carcinogenesis is a multi-step process, often involving the appearance of several new cell populations between the initial target cells and the ultimate cancer4,5, it is possible that the regenerative response of liver following PH could have a major effect on one or more steps subsequent to initiation. Thus, the use of a very late end-point (cancer) makes it difficult, if not impossible, to relate with any accuracy some very early event to any specific step in the carcinogenic process. Solt and Farber6 have recently developed a new approach to the sequential analysis of carcinogenesis in vivo that delineates the first few steps in the process and is a quantitative assay for initiation of liver cancer. We have used this model to investigate whether cell replication exerts its first effect on initiation or on some later step in the carcinogenic process. And if initiation is at least one site of action, when in the regenerative cell cycle is a carcinogen most effective and what biochemical events might be involved at this phase of the cell cycle?
339 citations
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TL;DR: The control of proliferation of mesoderm-derived cells by EGF and FGF has been examined taking, as an example, the vascular endothelium.
Abstract: The control of proliferation of mesoderm-derived cells by EGF and FGF has been examined taking, as an example, the vascular endothelium. The mechanisms by which cell proliferation can be brought to a stop in vivo and in vitro have been reviewed.
323 citations
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TL;DR: It is concluded slight activity of endogenous sterol synthesis, which provides enfogenous copounds generated from meavalonate, may be essential to the growth of cells even when sufficeient amounts of cholesterol are availavel to the cells.
Abstract: Effects of ML-236B, a potent competiove inhibitor 3-hydrocy-3-methyglutaryl-CoA reductase, on the lipiod metabolism were studied using mouse L cells and human smin fibrobalsts. ML-236B completely inhibited sterol sythesis from both [14C]acetate and [14C]octanoate in these cells at a tconcentration of 0.5 μg/ml (11.117 μM). withour affecting thqat form [14C]mevalonate. Syntheses of other lipids adn macromolecules like DNA, RNA and protein were not affected at concentrations up to 5 μg/ml. Concentrations of ML-236B giving 50% inhibitionof sterol synthesis for [14C]acetate were as low homozygote with familial hypercholesteroloemia. The ML-236B-mediated inhibition of sterol syunthesis was readitly reversivle. The complkete inhibition of endogenous sterol synthesis at a higher concentration (5μg/ml) of ML-236-B caused a marked inhibition of cell growth even in the presence of exogenous cholesterol contained in while gfatel calf serum as lipoproteins. This inhivition of growth was prevented by teh presence in the culture medium of mevalonate, but not by acetate, thus indficating that ML-236B inhibit cell growth by specifically interferring with mevalonate wynthesis. It is further concluded thjat slight activity of endogenous sterol synthesis, which provides enfogenous copounds generated from meavalonate, may be essential to the growth of cells even when sufficeient amounts of cholesterol are availavel to the cells.
242 citations
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TL;DR: The effects of providing low oxygen tension in the gas phase of two different types of cell culture systems were investigated and the increased efficiency of colony formation was observed both with mouse and human marrow cells.
Abstract: The effects of providing low oxygen tension in the gas phase of two different types of cell culture systems were investigated. The clonal growth of granulocyte-macrophage progenitor cells in an agar culture system was improved markedly by incubation within a low oxygen tension gas phase (48 mmHg--6.8%) instead of the conventional air (135 mmHg--19%), the effects being measured by increases in numbers of colony forming cells detected and in the colony sizes. The increased efficiency of colony formation was observed both with mouse and human marrow cells. A similar effect was observed in a liquid adherence culture system with primary cultures of foetal mouse fibroblasts both at clonal and higher cell densities.
238 citations
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TL;DR: Plasma components and the platelet-derived growth factor acted in a coordinate fashion to regulate the proliferation of Swiss 3T3 cells.
Abstract: DNA synthesis and cell division were measured in Swiss mouse 3T3 cells cultured in different concentrations of cell-free plasma-derived serum and increasing amounts of a platelet-derived growth factor In plasma-derived serum alone, the cells were quiescent and they were arrested in the Go/G1 phase of the cell cycle Addition of a platelet-derived growth factor to quiescent cells maintained in plasma-derived serum stimulated both DNA synthesis and cell division When plasma components were present at high concentration (5%, vol/vol), the amount of platelet factor added to the cultures determined the number of cell doublings Plasma-derived molecules were required for the platelet factor to stimulate DNA synthesis and cell division in the maximal number of cells In addition, plasma components had to be present for recently divided cells to respond to the platelet factor When 3T3 cells were cultured in excess platelet factor and limiting amounts of plasma-derived serum (05%, vol/vol), the cells underwent one doubling and then ceased to proliferate Addition of fresh plasma-derived serum to these cells induced a second round of cell division Plasma components and the platelet-derived growth factor acted in a coordinate fashion to regulate the proliferation of Swiss 3T3 cells
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TL;DR: A protein from normal uninfected avian cells that is antigenically related to the pp60 src viral protein responsible for transformation by ASV is identified and characterized.
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TL;DR: Experiments probing the mechanism by which glucocorticoids modulate cell proliferation were carried out on serum-free cell cultures of quiescent human diploid foreskin (HF) cells, suggesting a relationship between the dexamethasone effects on binding and growth.
Abstract: Experiments probing the mechanism by which glucocorticoids modulate cell proliferation were carried out on serum-free cell cultures of quiescent human diploid foreskin (HF) cells. Added alone, the synthetic glucocorticoid dexamethasone had no effect on cell number. However, dexamethasone enhanced the mitogenic response of HF cells to epidermal growth factor (EGF) by 50% at all EGF concentrations. The mitogenic action of EGF was maximally promoted by a dexamethasone concentration of 100 ng/ml (0.25 μM). Binding studies with 125 I-labeled EGF ( 125 I-EGF) suggested that dexamethasone caused this “permissive” effect by modulating cell surface receptors for EGF. Paralleling their increased responsiveness to EGF growth stimulation, dexamethasone-treated cells exhibited a 50-100% increased ability to bind physiological concentrations of 125 I-EGF. A binding increase was apparent after a 4-hr dexamethasone treatment. The dexamethasone-treated cells maintained an increased ability to bind 125 I-EGF during the prolonged exposure to EGF that was required to stimulate cell division. Moreover, the increase in 125 I-EGF binding exhibited a dexamethasone dose-dependence similar to that for the enhancement of EGF mitogenesis, suggesting a relationship between the dexamethasone effects on binding and growth. An investigation of the binding increase showed that it was specific for glucocorticoids, and required protein synthesis. The enhancement of 125 I-EGF binding diminished with increasing concentrations of 125 I-EGF, indicating that dexamethasone caused a qualitative change in the EGF receptors (possibly a change in receptor affinity or cooperativity). The alteration in 125 I-EGF binding may occur as part of a far-reaching dexamethasone-mediated change in the cell surface, because dexamethasone treatment slightly increased the ability of HF cells to bind 125 I-insulin, and decreased by half their ability to bind 125 I-thrombin.
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TL;DR: Twenty-five mutants altered in this control have been isolated which have the same growth rate as wild type but divide at a smaller cell size.
Abstract: The control co-ordinating cell division with cell growth has been investigated in the fission yeast Schizosaccharomyces pombe Twenty-five mutants altered in this control have been isolated which have the same growth rate as wild type but divide at a smaller cell size The mutants define two genes wee 1 and wee 2, both of which are involved in a control initiating mitosis when the cell attains a critical size
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TL;DR: Addition of the anti-estrogen, Tamoxifen (10(-6) M), inhibited cells below the growth rate seen when estradiol was omitted from the medium, thus suggesting an action of Tamxifen which may be independent of competition with estradio.
Abstract: ZR-75-1, a human breast cancer cell line, has been grown in hormone-supplemented medium without serum. The factors required for optimal growth include 17β-estradiol, insulin, transferrin, dexamethasone, and l-triiodothyronine. If estradiol, insulin, or l-triiodothyronine is omitted, cells cease division within 7 days, but viability is retained for at least 14 days. Omission of transferrin leads to cell death within 7 days. The cells have been continuously maintained in this environment without morphological alteration or cessation of growth for more than 5 months. Addition of the anti-estrogen, Tamoxifen (10-6m), inhibited cells below the growth rate seen when estradiol was omitted from the medium, even when Tamoxifen was added 4 days and two medium changes after the removal of estradiol from the medium, thus suggesting an action of Tamoxifen which may be independent of competition with estradiol. The availability of a human breast cancer cell line that can be propagated in hormone-supplemented medium without serum should aid in the study of the mechanisms by which hormones effect cell growth.
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TL;DR: The available data do not permit assessment of genetic damage in the offsprings of BLM-treated patients, and it is concluded that the genetic effects of BLM can be modified quantitatively by thiol compounds, caffeine, hyperthermia and H2O2.
Abstract: Bleomycin (BLM), an antibiotic obtained from Streptomyces verticillus, is of significance as an antineoplastic agent. The compound is actually the mixture of some 200 related forms which differ from each other in the amine moiety. The drug, at low concentrations, can cause elimination of bases, particularly thymine. This causes strand breakage of DNA and inhibition of cell growth. The influence of BLM on cell growth may be unrelated to the effects on DNA. In general, mitotically dividing cells show more DNA damage than non-dividing cells. G2 seems to be the most sensitive phase indicating that cell death may not be related to a direct effect of BLM on DNA replication. The antibiotic shows specific effects on chromatin and causes chromosomal damage in all sub-phases of interphase. It can affect early prophase chromosomes also. Suggestion has been made that BLM-induced breakage and cell death are similar to those induced by densely ionizing radiations. Whereas the antibiotic affects the frequency of somatic crossing over and produces micronuclei, the data on mutation induction and production of sister-chromatid exchanges do not permit classifying BLM as a potent inducer of these phenomena. The genetic effects of BLM can be modified quantitatively by thiol compounds, caffeine, hyperthermia and H2O2. It is concluded that the available data do not permit assessment of genetic damage in the offsprings of BLM-treated patients. Such studies are urgently needed, as are the studies to find out the effects of BLM on meiotic phenomena.
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TL;DR: The addition of heat‐treated extracts of human platelets to PPP‐supplemented medium stimulated the replication of both the normal mouse cells and early passage human embryo fibroblasts.
Abstract: Early passage mouse embryo fibroblasts, mouse 3T3 cell lines, and early passage diploid human fibroblasts grew to higher cell densities in tissue culture medium supplemented with serum than in medium supplemented with defibrinogenated platelet-poor plasma (PPP). Unlike the mouse cells, the human fibroblasts displayed this differential growth response only in the presence of hypophysiologic concentrations of calcium. The addition of heat-treated extracts of human platelets to PPP-supplemented medium stimulated the replication of both the normal mouse cells and early passage human embryo fibroblasts.
Human or mouse fibroblasts transformed by either retroviruses or by SV40, including SV40 infected “serum revertants” and “flat transformants,” grew to equal cell densities in medium supplemented with either serum or PPP. Infection of Balb/c-3T3 cells with SV40 rapidly induced them to grow in PPP-supplemented medium demonstrating that the ability of SV40-transformed cell lines to proliferate in PPP-supplemented medium does not arise from the cell culture selection procedures usually employed to obtain stable virus-transformed cell lines. 3T3 cells infected but not transformed by retroviruses do not replicate in PPP-supplemented medium demonstrating that reduction of the growth requirement for the platelet growth factor(s) by retroviruses is a transformation-specific response. Cell cultures that did not proliferate well in PPP-supplemented medium did not form tumors when inoculated into athymic nude mice. Many, although not all, of the lines which grew well in PPP medium were tumorigenic in nude mice. Together, these findings indicate that: (1) normal fibroblast-like cells display a growth requirement for factor(s) present in serum but not found in PPP; (2) this serum specific growth factor is derived from platelets; (3) a primary response to viral transforming genes is a reduction in the growth requirement for these platelet-derived factors; and (4) cells that have a reduced requirement for the platelet-derived growth factor are often tumorigenic.
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TL;DR: It is shown that, in vitro, the morphology of epithelial cells can be modified by a retinal extract (RE) and that the latter also contains a potent growth-promoting factor.
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TL;DR: Kinetic changes caused by hormones have profound implications in clinical therapy, since the efficacy of cycle active agents may be altered.
Abstract: The effect of 17β-estradiol on an estrogen receptor-positive human breast cancer cell line (MCF-7) was studied. Low concentrations (10 -9 m) of 17β-estradiol enhanced the rate of cell proliferation; the overall cell cycle time was shortened; and the proportion of cells in the S phase increased. Higher concentrations (10 -7 m) suppressed proliferation and slightly decreased the proportion of cells in DNA synthesis. When combined with 1-β-d-arabinofuranosylcytosine, an S-phase-specific chemotherapeutic agent, 10 -9 m 17β-estradiol enhanced cell killing. This enhancement was not observed with 10 -7 m 17β-estradiol. Kinetic changes caused by hormones have profound implications in clinical therapy, since the efficacy of cycle active agents may be altered.
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TL;DR: It is reported here that culturing NIL or 3T3 cells in vitamin A-containing medium markedly enhances, whereas a medium with ultraviolet-irradiated serum markedly reduces, contact orientation and cell-density dependent inhibition of cell growth.
Abstract: CHEMICAL carcinogenesis and viral transformation are prevented or inhibited by vitamin A or its analogues1,2. Vitamin A may also play a part in membrane glycosylation as a lipid intermediate3,4. Recently, effects of retinoic acid on proliferation and density-dependent growth of mouse L cells5 and many other untransformed and transformed cells in vitro have been described6. In view of these observations, we have studied the effect of retinol on cell growth behaviour, glycolipid synthesis, and surface-exposed profile of glycoproteins in hamster fibroblasts NIL, NILpy and mouse (BALB/c) 3T3 cells. We report here that culturing NIL or 3T3 cells in vitamin A-containing medium markedly enhances, whereas a medium with ultraviolet-irradiated serum markedly reduces, contact orientation and cell-density dependent inhibition of cell growth. Associated changes of cell surface membrane GM3 level, ganglioside contact response, and in LETS (‘Gap a’) were observed.
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TL;DR: Some properties of growth factors produced by this human tumour cell line, derived from a 25-yr-old female with fibrosarcoma of the leg, are described.
Abstract: WE suggested previously that transformed cells may produce and release cellular growth factors capable of interacting with a specific class of cellular receptors, making them unavailable as receptors for external ligands1,2. A prediction of this model was that a human fibrosarcoma line, which had been shown not to bind 125I-labelled multiplication stimulating activity (MSA)2, might be secreting molecules functionally related to MSA. We describe here some properties of growth factors produced by this human tumour cell line, derived from a 25-yr-old female with fibrosarcoma of the leg. The cells produce a family of MSA-related compounds with different molecular weights that can be separated on Sephadex G-75. The major activities correspond to proteins of approximate molecular weight (MW) of 11,000 and 7,000. Both of these fractions stimulate cell division, and will compete with 125I-labelled MSA for its receptors on mouse, rat or human cell membranes. Fibrosarcoma cells in culture may constitute an important alternate source to human serum and plasma for the isolation and characterisation of growth stimulating factors.
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TL;DR: Mesenchyme cells derived from limb buds of day 10 mouse embryos were plated out at confluent and sub-confluent cell densities and vitamin A did not inhibit growth in sub- confluent cultures, suggesting that vitamin A may inhibit growth by causing contact inhibition.
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TL;DR: The precursor cells which give rise to the ventral nerve cord have been studied in lin-5 and in the mutant these precursors accumulate approximately six times the diploid quantity of DNA within a single nucleus, while attempting mitosis up to three times.
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TL;DR: The results indicate that the effect of E. coli L‐asparaginase on cultured pancreatic carcinoma cells is exerted at least in part through its L‐glutaminase activity.
Abstract: The effects of E. coli L-asparaginase on cultured human pancreatic carcinoma (MIA PaCa-2) have been studied. The enzyme (1 U/ml) inhibited growth and protein synthesis in both MIA PaCa-2 and PANC-1, another pancreatic carcinoma cell line, but had little or no effect on human breast carcinoma or melanoma cells. The inhibition of protein synthesis by E. coli L-asparaginase was largely reversed by L-glutamine but not by L-asparagine. The growth of both MIA PaCa-2 and PANC-1 showed absolute dependence on L-glutamine. These results indicate that the effect of E. coli L-asparaginase on cultured pancreatic carcinoma cells is exerted at least in part through its L-glutaminase activity. Although the addition of L-glutamine to the culture appeared to prevent cell death caused by L-asparaginase, it did not restore the ability of the cells to proliferate. Asparaginase derived from vibrio succinogenes, which is virtually free of L-glutaminase activity, was equally inhibitory to MIA PaCa-2 cell growth but did not affect protein synthesis. It is concluded that the inhibition of growth of cultured pancreatic carcinoma cells by E. coli asparaginase is a combined function of both its L-asparaginase and L-glutaminase activity.
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09 Jun 1978TL;DR: In this article, a process for the in-vitro biosynthesis of hormones, especially of insulin, was described by in vitro conservation of cells from organs and tissues of animal or human origin under suitable cell growth and cell conservation conditions and isolation of the substance formed in a known manner from the culture medium or by processing of the cells.
Abstract: Process for the in-vitro biosynthesis of hormones, especially of insulin, by in-vitro conservation or in-vitro propagation of cells from organs and tissues of animal or human origin under suitable cell growth and cell conservation conditions and isolation of the substance formed in a known manner from the culture medium or by processing of the cells. The hormone-producing cells are propagated or conserved in one or more cell culture spaces separated by semipermeable flat membranes of at least one culture medium space.
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TL;DR: Addition of spermidine or spermine to MGBG‐arrested REF cells results in a rapid resumption of proliferation demonstrating that either polyamine can fulfill the role played by these polyamines in the growth process.
Abstract: Following growth stimulation of rat embryo fibroblast (REF) cells previously arrested in G1 by serum deprivation, there occurs a large increase in the synthesis of the polyamines putrescine, spermidine and spermine. Methylglyoxal bis(guanylhydrazone) (MGBG), a potent inhibitor of S-adenosylmethionine decarboxylase can block the accumulation of both spermidine and spermine over a period of several days. Under such conditions REF cells treated with MGBG will approximately double in number and then become growth-arrested again predominantly in the G1 phase of the cell cycle. REF cells therefore appear to contain sufficient spermidine and spermine to progress through one cell cycle before the intracellular levels of these polyamines is reduced sufficiently to arrest growth in the absence of continued polyamine synthesis. Limitation of intracellular polyamine levels is therefore not the mechanism by which deprivation of serum growth factors arrests cell growth. While continued growth is nevertheless dependent on polyamine synthesis, this cell type is capable of limited proliferation in its absence. Addition of spermidine or spermine to MGBG-arrested REF cells results in a rapid resumption of proliferation demonstrating that either polyamine can fulfill the role played by these polyamines in the growth process. Low levels of spermidine and spermine therefore arrest this cell type at a resriction point in G1 at which it is decided whether the intracellular level of these polyamines is sufficiently high to enable a cell to enter into and complete a new cell cycle. This polyamine-sensitive restriction point is considered to be analogous to the restriction point(s) in G1 at which serum and nutrient limitation act.
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TL;DR: The rate of protein degradation was found to be a relatively invariant parameter that did not change after strong inhibition of protein synthesis with cycloheximide or histidinol, it was the same in both exponential and stationary phase, and it did not correlate with the presence or absence of malignant tranformation.
Abstract: The role of protein degradation in cellular proliferation was investigated by measurements of the rates of degradation of labile and stable proteins for a number of cell types under various growth conditions. The rate of protein degradation was found to be a relatively invariant parameter in that it did not change after strong inhibition of protein synthesis with cycloheximide or histidinol, it was the same in both exponential and stationary phase, and it did not correlate with the presence or absence of malignant tranformation.
Using three different cell types with widely differing division rates, the rate of cell division and DNA synthesis (in %/hr) was found to be precisely equal to the rate of protein accumulation (in %/hr), i.e., to the rate of protein synthesis minus the rate of protein degradation. Division rates between the different cell types appeared to be determined chiefly by the rate of protein synthesis though, especially at low division rates, the rate of protein degradation could represent a large component of the protein accumulation rate.
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TL;DR: It is reported here that the mutant AD6 cells show a dramatic decrease in EGF binding, whereas their ability to bind insulin is normal, which is consistent with the notion that the receptor for EGF is a glycoprotein.
Abstract: THE surface of animal cells contains a variety of complex macromolecules, some of which modulate cell growth, adhesion and motility. A number of peptide hormones and growth factors influence cellular proliferation and macromolecular synthesis with binding to surface proteins of responsive cells as the first phase of their action1–4. The structure and identity of these receptor molecules is a topic of widespread interest. Epidermal growth factor (EGF) is a low molecular weight peptide (MW 6,000) capable of stimulating DNA synthesis and proliferation in epidermal cells5, human fibroblasts6, and mouse embryo fibroblasts (3T3)7. It has also been reported to stimulate the synthesis of a major cell surface glycoprotein (CSP)8 and hyaluronic acid9 in 3T3 cells and human fibroblasts maintained in low serum. These effects occur at extremely low concentrations of EGF, in the ng ml−1 range, and the first step in this process is the specific binding to surface receptors, followed by rapid internalisation and degradation10. Pouyssegur and Pastan11 have isolated a nontransformed mutant (AD6) of BALB/c 3T3 cells that has a dramatic decrease in cell surface carbohydrates due to a specific, but partial block in the acetylation of N-acetylglucosamine-6-phosphate. This early defect in the biosynthesis of amino sugars leads to incomplete glycosylation of glycoproteins and to decreased exposure of glycoproteins on the cell surface12. Culturing the cells in the presence of N-acetylglucosamine (GlcNAc) bypasses the enzymatic block and results in a restoration of altered surface components13. We report here that the mutant AD6 cells show a dramatic decrease in EGF binding, whereas their ability to bind insulin is normal. Our data are consistent with the notion that the receptor for EGF is a glycoprotein.
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TL;DR: Since antagonists of growth factors are probably as important as the mitogens in the overall control of cell proliferation, certain mechanisms and agents through which the mitogenic effect of FGF can be repressed are reviewed, i.e., cell-cell interaction at confluence, trophic hormones, and a diffusible factor from cartilage.
Abstract: Recent studies on the effect of the fibroblast and epidermal growth factors (FGF and EGF, respectively) on the proliferation of ovarian cells and vascular endothelial cells are reviewed. During the ovarian cycle, luteal cells are derived from granulosa cells by a process of cytomorphosis. These two cell types thus allow a study of the changes that occur in growth control when one cell type is converted into another. Also described is the control of vascular endothelial cell proliferation by FGF (but not by EGF). We discuss the effects of FGF and EGF on cells derived from the embryonic ectoderm, mesoderm, and endoderm and examine the hypothesis that cellular specificity for various growth factors is conferred during embryo development. Finally, since antagonists of growth factors are probably as important as the mitogens in the overall control of cell proliferation, we review certain mechanisms and agents through which the mitogenic effect of FGF can be repressed, i.e., cell-cell interaction at confluence, trophic hormones, and a diffusible factor(s) from cartilage.