Regulation of epithelial proliferation by TGF-beta.
The closely related mammalian TGF-betas (TGF-beta 1, TGF-beta 2 and TGF-beta 3) are potent inhibitors of proliferation of many cell types in vitro. TGF-beta 1 has been demonstrated to be growth inhibitory in vivo for epithelial, endothelial, myeloid and lymphoid cells. Utilizing skin keratinocytes as a model system for studying the mechanism of TGF-beta 1-induced growth inhibition, it has been demonstrated that TGF-beta 1 rapidly inhibits transcription of the c-myc gene. Antisense c-myc oligonucleotides inhibit proliferation of keratinocytes as effectively as does TGF-beta 1, indicating that TGF-beta 1 suppression of c-myc expression is an important component of this growth inhibition. Studies utilizing DNA tumour virus transforming gene constructs have shown that the retinoblastoma gene product, pRb, or a related protein, is needed for TGF-beta 1 suppression of c-myc transcription. Thus, TGF-beta 1 may act through a tumour suppressor gene product, pRb, to suppress transcription of a proto-oncogene, c-myc, and subsequently inhibit cell proliferation.
Moses
H L
HL
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Yang
E Y
EY
Pietenpol
J A
JA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004263:DNA Tumor Viruses / Q000502:physiology; D003864:Depression, Chemical; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D009857:Oncogenes / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D016160:Retinoblastoma Protein / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta