Showing papers by "Ira Pastan published in 1972"
TL;DR: Growth stops at confluency in mouse 3T3 cells and in MA308 human diploid fibroblasts even with frequent changes of media and supports the proposal that cyclic AMP regulates cell growth and mediates contact inhibition of growth.
284 citations
TL;DR: At present, no strong evidence connects contact inhibition of movement and growth, but as transformation often disturbs both properties a connexion between them may exist.
Abstract: FIBROBLASTS exhibit a locomotory behaviour in cultures on a plane surface. An undulating membrane or leading lamella forms at the frontal edge and may be the locomotory organ of the cell. When the leading lamellae of two cells collide, several events occur. The forward motion of the cells is stopped, the cells contract, the undulations of the membrane cease, and movement proceeds in a different direction. This has been termed contact inhibition of movement1. When cells become confluent, movement is considerably decreased, presumably due to contact on all surfaces, and at confluency there are restrictions on cell growth which are apparently related to the population density of the cells. This has been termed contact or density-dependent inhibition of growth2–4. At present, no strong evidence connects contact inhibition of movement and growth, but as transformation often disturbs both properties a connexion between them may exist3,5.
161 citations
TL;DR: It is concluded that intracellular concentrations of cAMP regulate the synthesis ofcAMP-phosphodiesterase, and that cAMP functions as an inducer of the enzyme.
Abstract: Cyclic AMP-phosphodiesterase is present in various mouse fibroblasts. Contact-inhibited 3T3 cells contain two forms of the enzyme, one with a Km of 2.5 μM and the second with a Km of 71 μM. As 3T3 cells grow to confluency and cAMP concentrations rise, the activity of the first enzyme increases, whereas that of the second is unchanged. A line of SV40-transformed 3T3 cells with low cAMP concentration also has low levels of the cAMP-phosphodiesterase with a Km of 2.5 μM. Treatment of 3T3 and SV40-transformed 3T3 cells with dibutyryl cAMP and theophylline increases cAMP-phosphodiesterase accumulation. This accumulation is blocked by cycloheximide and actinomycin D. The newly formed enzyme resembles the higher affinity enzyme present in unstimulated cells, since it has a Km of 1.2-2.0 μM, and is stimulated by snake venom. In L cells in which cAMP concentrations are elevated by treatment with prostaglandin E1, cAMP phosphodiesterase also accumulates. We conclude that intracellular concentrations of cAMP regulate the synthesis of cAMP-phosphodiesterase, and that cAMP functions as an inducer of the enzyme.
131 citations
TL;DR: Chicken embryo fibroblasts infected with a temperature-sensitive mutant of Rous sarcoma virus (RSV-Ta) have normal morphology at 40.5° but after a transfer to 36° show the morphological characteristics of transformed cells, suggesting that an early event in transformation leads to a decreased level of cyclic AMP.
126 citations
TL;DR: It is found that during treatment with dibutyryl cyclic AMP, melanoma cells spread out, appear larger and produce considerably more pigment than untreated cells.
Abstract: IN VITRO studies have suggested that adenosine 3′,′-monophosphate (cyclic AMP) regulates cell morphology. During treatment with the dibutyryl analogue of cyclic AMP, N6,O2′-dibutyryl cyclic AMP, transformed fibroblasts acquire several morphological characteristics of untransformed fibroblasts1,3. Cell processes are extended, the cells occupy a greater surface area and in some cases there is a parallel alignment of cells. Chinese hamster ovary cells are affected in the same way. In neuroblastoma cells5, dibutyryl cyclic AMP induces neurite extension and increases the activity of acetylcholinesterase, an indicator of biochemical differentiation6. Cyclic AMP is known to control the dispersion of melanin7,8 and the differentiation of melanoblasts into melanocytes. We have now found that during treatment with dibutyryl cyclic AMP, melanoma cells spread out, appear larger and produce considerably more pigment than untreated cells.
122 citations
TL;DR: The results suggest that cyclic AMP has at least three regulatory functions during the cell cycle, two negative and one positive, and indicates the presence of a cyclicAMP-dependent block in G2.
111 citations
106 citations
TL;DR: The interaction between the cell surface and the substratum is very important in determining several characteristics of cells growing in tissue culture and this reduced interaction may be responsible for abnormal properties such as the loss of contact or density dependent inhibition of growth.
Abstract: THE interaction between the cell surface and the substratum is very important in determining several characteristics of cells growing in tissue culture. Transformed cells are less adherent to the substratum than untransformed cells1 and this reduced interaction with the substratum may be responsible for abnormal properties such as the loss of contact or density dependent inhibition of growth2 and the ability to form colonies in agar and to grow in suspension culture.
98 citations
TL;DR: Comparison of the rate of sulfate incorporation into acid mucopolysaccharides from the cells indicated that the effect was due to a greater rate of synthesis of these compounds at the time of labeling rather than due to to a decrease in the rates of their degradation.
93 citations
TL;DR: Fibroblast myOSin appears to be similar to muscle myosin in structure and function.
Abstract: Myosin has been isolated from cloned mouse fibroblasts, line L-929 Fibroblast myosin: (i) binds to rabbit muscle actin and is dissociated from it by ATP, (ii) has an ATPase activity that is suppressed by Mg2+ in 06 M KCl and is activated by rabbit muscle actin in the presence of Mg2+ in 14 mM KCl, (iii) forms thin bipolar aggregates in 01 M KCl when viewed in the electron microscope, (iv) possesses a heavy chain with the same mobility as muscle myosin (molecular weight 200,000) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis In these respects, fibroblast myosin appears to be similar to muscle myosin in structure and function
84 citations
TL;DR: Although CRP binds to DNA species containing no known CRP-cyclic AMP sensitive promoters, the cyclicAMP dependency of the binding suggests that DNA binding of CRP may be important in stimulation of transcription by CRP -cyclic AmP.
01 Jan 1972
TL;DR: The use of N6,O2'-dibutyryl 3’,5’-adenosine monophosphate (dbc-AMP) has demonstrated that cyclic AMP regulates several functions of fibroblasts, which are of obvious inportance to cancer research.
Abstract: The use of N6,O2’-dibutyryl 3’,5’-adenosine monophosphate (dbc-AMP) has demonstrated that cyclic AMP regulates several functions of fibroblasts (Table I) (Johnson et al, 1971a and 1971b; Sheppard, 1971; Hsie and Puck, 1971), Since these functions are frequently altered by transformation, the regulation of cyclic AMP metabolism is of obvious inportance to cancer research.
01 Jan 1972