Selective inhibition of growth-related gene expression in murine keratinocytes by transforming growth factor beta.
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.
Coffey
R J
RJ
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Bascom
C C
CC
Sipes
N J
NJ
Graves-Deal
R
R
Weissman
B E
BE
Moses
H L
HL
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D000078404:Epidermal Cells; D006131:Growth Inhibitors / Q000494:pharmacology*; D007633:Keratins; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009693:Nucleic Acid Hybridization; D011519:Proto-Oncogenes; D012313:RNA / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*; D015291:Transforming Growth Factors / Q000494:pharmacology*
D006131:Growth Inhibitors; D012313:RNA; D007633:Keratins; D015291:Transforming Growth Factors