Selective inhibition of growth-related gene expression in murine keratinocytes by transforming growth factor beta.

Coffey RJ, Bascom CC, Sipes NJ, Graves-Deal R, Weissman BE, Moses HL
Mol Cell Biol. 1988 8 (8): 3088-93

PMID: 2463471 · PMCID: PMC363535

Transforming growth factor beta (TGF beta) is a potent inhibitor of epithelial cell proliferation. A nontumorigenic epidermal growth factor (EGF)-dependent epithelial cell line, BALB/MK, is reversibly growth arrested by TGF beta. TGF beta will also abrogate EGF-stimulated mitogenesis of quiescent BALB/MK cells. Increased levels of calcium (greater than 1.0 mM) will induce differentiation in BALB/MK cells; in contrast, TGF beta-mediated growth inhibition does not result in induction of terminal differentiation. In the present study, the effects of TGF beta and calcium on growth factor-inducible gene expression were examined. TGF beta markedly decreased c-myc and KC gene expression in rapidly growing BALB/MK cells and reduced the EGF induction of c-myc and KC in a quiescent population of cells. TGF beta exerted its control over c-myc expression at a posttranscriptional level, and this inhibitory effect was dependent on protein synthesis. TGF beta had no effect on c-fos gene expression, whereas 1.5 mM calcium attenuated EGF-induced c-fos expression in quiescent cells. Expression of beta-actin, however, was slightly increased in both rapidly growing and EGF-restimulated quiescent BALB/MK cells treated with TGF beta. Thus, in this system, TGF beta selectively reduced expression of certain genes associated with cell proliferation (c-myc and KC), and at least part of the TGF beta effect was at a posttranscriptional level.

MeSH Terms (16)

Animals Cell Division Cell Nucleus Cells, Cultured Epidermal Cells Growth Inhibitors Keratins Kinetics Mice Mice, Inbred BALB C Nucleic Acid Hybridization Proto-Oncogenes RNA RNA Processing, Post-Transcriptional Transcription, Genetic Transforming Growth Factors

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