1,721,081 research outputs found
From growth arrest to growth suppression
No full textSince the introduction of the cell cycle concept two approaches to study growth regulation of cells have been proposed. One claims that cells are naturally quiescent, requiring a stimulatory encouter with growth factors for induction of cell division. The other considers cellular multiplication as the natural steady-state; cessation of multiplication is thus a restriction imposed on the system. In the latter case emphasis is mainly on the signals involved in arrest of multiplication. This Prospect focuses on specific events occurring in mammalian cells at growth arrest, senescence, and terminal differentiation, specifically emphasizing the growth inhibitory factors, tumor suppressor genes, and other signals for growth suppression
Regulation of expression of growth arrest-specific genes in mouse fibroblasts
No full textThe suppression of growth arrest-specific (gas) gene expression by serum appeared to be independent of protein synthesis, but expression in resting cells was sensitive to 2-aminopurine, an inhibitor of intracellular protein kinases. Although accumulation of gas gene mRNA was reduced by serum, nuclear transcription of the gas-2, -3, and -5 genes was observed in serum-stimulated cells, indicating that posttranscriptional events may regulate mRNA levels. Growth induction by serum, on the other hand, led to suppression of transcription of the gas-1 gene. Cell cycle regulation and the serum response of gas-1 were lost in ras-transformed cells
Regulation of expression of growth arrest-specific genes in mouse fibroblasts
No full textThe suppression of growth arrest-specific (gas) gene expression by serum appeared to be independent of
protein synthesis, but expression in resting cells was sensitive to 2-aminopurine, an inhibitor of intracellular
protein kinases. Although accumulation of gas gene mRNA was reduced by serum, nuclear transcription of the
gas-2, -3, and -5 genes was observed in serum-stimulated cells, indicating that posttranscriptional events may
regulate mRNA levels. Growth induction by serum, on the other hand, led to suppression of transcription of
the gas-i gene. Cell cycle regulation and the serum response of gas-l were lost in ras-transformed cells
The growth-inhibitory block of TGF-beta is located close to the G1/S border in the cell cycle
No full textTransforming growth factor-beta (TGF-beta) inhibits DNA synthesis in dense cultures of young human embryonic fibroblasts and antagonizes the mitogenic action of platelet-derived growth factor (PDGF). The inhibition of the PDGF-BB action by TGF-beta was independent of the induction of mRNAs for the PDGF-A chain and PDGF-beta receptor, the predominant types of PDGF receptor in human fibroblasts. The TGF-beta-mediated inhibition did not influence the expression of various genes that are involved in the transition from the arrested (GO) state to the S phase of the cell cycle. Indeed, TGF-beta upregulated the "early" genes c-myc, c-fos, and junB and downregulated the growth arrest-specific (gas) genes. These results suggest that the inhibition of DNA synthesis by TGF-beta in human fibroblasts is independent of modulation of expression of early and gas genes, placing the TGF-beta block comparatively late in the GO to S transition. In cultures of senescent human fibroblasts TGF-beta stimulated DNA synthesis but, nevertheless, had the same effect as in young cells on the expression of PDGF chains and receptor genes, as well as on early and gas genes, with the exception of a significantly lower induction of c-fos
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