Cell growth

About: Cell growth is a research topic. Over the lifetime, 104237 publications have been published within this topic receiving 3751303 citations. The topic is also known as: GO:0016049 & cellular growth.

Stromal Cell-derived Factor 1α Stimulates Human Glioblastoma Cell Growth through the Activation of Both Extracellular Signal-regulated Kinases 1/2 and Akt

Abstract: In this paper, we describe the role of chemokine receptor CXCR4 activation by its natural ligand, the chemokine stromal cell-derived factor (SDF-1) (CXCL12), in glioblastoma cell growth in vitro. We show that both CXC chemokine receptor 4 (CXCR4) and SDF-1 mRNA are expressed in several human glioblastoma multiforme tumor tissues and in two human glioblastoma cell lines, U87-MG and DBTRG-05MG. These cells are able to secrete SDF-1 under basal conditions, and the rate of secretion is highly increased after lipopolysaccharide or 1% fetal bovine serum treatment. Exogenous SDF-1alpha induces proliferation in a dose-dependent manner in both cell lines. Moreover, we observed that SDF-1alpha-dependent proliferation is correlated with phosphorylation and activation of both extracellular signal-regulated kinases 1/2 and Akt and that these kinases are independently involved in glioblastoma cell proliferation. The role of CXCR4 stimulation in glioblastoma cell growth is further demonstrated by the ability of human monoclonal CXCR4 antibody (clone 12G5) to inhibit the SDF-1alpha-induced proliferation as well as the proliferation induced by SDF-1-releasing treatments (lipopolysaccharide and 1% fetal bovine serum). These data support a role for SDF-1alpha in the regulation of glioblastoma growth in vitro, likely through an autocrine/paracrine mechanism.

Human homolog of fission yeast cdc25 mitotic inducer is predominantly expressed in G2

Abstract: Entry into mitosis during the somatic cell cycle is regulated in response to signals that monitor the completion of DNA replication, the integrity of the nuclear genome, and, possibly, the increase in cellular mass during the cell cycle. It has been postulated that the operation of this cell cycle control involves the gradual accumulation of rate-limiting mitotic inducers, which trigger nuclear division when their cellular concentration reaches a critical level. We have cloned a human gene, which we call CDC25, whose product may function as a mitotic inducer. This human gene encodes a protein with a predicted molecular mass of 53,000 daltons whose C-terminal domain shares about 37% sequence identity with the fission yeast cdc25+ mitotic inducer. The human CDC25 gene rescues the defect of a fission yeast temperature-sensitive (ts) cdc25ts mutant that is unable to initiate mitosis. In HeLa cells CDC25 mRNA levels are very low in G1 and increase at least 4-fold as cells progress towards M phase. These data suggest that in human cells, as in fission yeast, the accumulation of CDC25 mitotic inducer during G2 may play a key role in regulating the timing of mitosis.

Suppression of cell growth and invasion by miR-205 in breast cancer

Abstract: MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB-231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR-205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A (VEGF-A) are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3′-untranslated region (3′-UTR) of ErbB3 and VEGF-A. Together, these results suggest that miR-205 is a tumor suppressor in breast cancer.

p38α suppresses normal and cancer cell proliferation by antagonizing the JNK–c-Jun pathway

Abstract: The mitogen-activated protein kinase (MAPK) p38alpha controls inflammatory responses and cell proliferation. Using mice carrying conditional Mapk14 (also known as p38alpha) alleles, we investigated its function in postnatal development and tumorigenesis. When we specifically deleted Mapk14 in the mouse embryo, fetuses developed to term but died shortly after birth, probably owing to lung dysfunction. Fetal hematopoietic cells and embryonic fibroblasts deficient in p38alpha showed increased proliferation resulting from sustained activation of the c-Jun N-terminal kinase (JNK)-c-Jun pathway. Notably, in chemical-induced liver cancer development, mice with liver-specific deletion of Mapk14 showed enhanced hepatocyte proliferation and tumor development that correlated with upregulation of the JNK-c-Jun pathway. Furthermore, inactivation of JNK or c-Jun suppressed the increased proliferation of Mapk14-deficient hepatocytes and tumor cells. These results demonstrate a new mechanism whereby p38alpha negatively regulates cell proliferation by antagonizing the JNK-c-Jun pathway in multiple cell types and in liver cancer development.

Mutants in the S. cerevisiae PKC1 gene display a cell cycle-specific osmotic stability defect.

Abstract: The PKC1 gene of Saccharomyces cerevisiae encodes a homologue of the Ca(2+)-dependent isozymes of mammalian protein kinase C (Levin, D.cE., F. O. Fields, R. Kunisawa, J. M. Bishop, and J. Thorner. 1990. Cell. 62:213-224). Cells depleted of the PKC1 gene product display a uniform phenotype, a behavior indicating a defect in the cell division cycle (cdc). These cells arrest division after DNA replication, but before mitosis. Unlike most cdc mutants, which continue to grow in the absence of cell division, PKC1-depleted cells arrest growth with small buds. We created conditional alleles of PKC1 to explore the nature of this unusual cdc defect. In contrast to PKC1-depleted cells, all of the conditional pkc1 mutants isolated were suppressed by the addition of CaCl2 to the medium, suggesting that the mutant enzymes could be activated by Ca2+. Arrest of growth and cell division in the conditional mutants was accompanied by cessation of protein synthesis, rapid loss of viability, and release of cellular material into the medium, suggesting cell lysis. This conclusion was supported by the observation that a pkc1 deletion mutant was capable of proliferation in osmotically stabilized medium, but underwent rapid cell lysis when shifted to hypo-osmotic medium. We have incorporated these observations into a model to explain the cdc-specific arrest of pkc1 mutants.