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Mol Reprod Dev. 1992 Jun;32(2):179-84.

TGF-beta regulation of epithelial cell proliferation.

Author information

1
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.

Abstract

The predominant effect of TGF-beta 1 on cell proliferation is inhibition. Earlier studies demonstrated that TGF-beta 1 inhibition of skin keratinocyte proliferation involves suppression of c-myc transcription and indirect evidence suggested that the protein product of the retinoblastoma gene (pRB) may be involved in this process. Skin keratinocytes transformed by SV40 and human papilloma virus-16 (HPV-16) or HPV-18 resisted growth inhibition and suppression of c-myc mRNA by TGF-beta. Transient expression of HPV-16 E7 gene, adenovirus E1A, and SV40 large T antigen (TAg) blocked the TGF-beta 1 suppression of c-myc transcription. Studies with transformation-defective mutants of E1A and TAg suggested that a cellular protein(s) that interacts with a conserved domain of the DNA tumor virus oncoproteins mediates TGF-beta 1 suppression of c-myc transcription and keratinocyte growth. Transient expression of pRB in skin keratinocytes repressed human c-myc promoter/CAT transcription as effectively as TGF-beta 1. The same c-myc promoter region, termed the TGF-beta Control Element (TCE), was required for regulation by both TGF-beta 1 and pRB. TCE bound a cellular protein of approximately 106 kDa and this binding was decreased by TGF-beta 1 treatment. Our data indicate that pRB can inhibit c-myc transcription and suggest the involvement of cellular factor(s) in addition to pRB in the TGF-beta 1 pathway for the suppression of c-myc transcription and growth inhibition.(ABSTRACT TRUNCATED AT 250 WORDS).

PMID:
1637556
DOI:
10.1002/mrd.1080320215
[Indexed for MEDLINE]

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