Regulation of transforming growth factor β1 gene expression by the product of the retinoblastoma-susceptibility gene

S. J. Kim, H. D. Lee, P. D. Robbins, K. Busam, M. B. Sporn, A. B. Roberts

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

Transforming growth factor β (TGF-β) isoforms inhibit the growth of many cell types and block progression of the cell cycle by inhibiting events in late G1 phase. The retinoblastoma gene product, RB, also has properties of a cell-cycle regulatory factor. It remains underphosphorylated in the presence of TGF-β and has been shown to repress the activity of the c-fos promoter, resulting in inhibition of transit through the cell cycle. These observations led us to examine effects of human RB on the expression of the human TGF-β1 gene. Using chimeric TGF-β1 promoter-chloramphenicol acetyltransferase gene constructs, we show that RB induces TGF-β1 gene expression in CCL-64 mink lung epithelial cells and A-549 human lung adenocarcinoma cells but represses its expression in NIH 3T3 and AKR-2B mouse cells. Several sequences homologous to the c-fos RB control element were identified in the TGF-β1 promoter. These results demonstrate that human RB can regulate TGF-β1 gene expression negatively or positively depending on the cell type.

Original languageEnglish (US)
Pages (from-to)3052-3056
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number8
DOIs
StatePublished - 1991
Externally publishedYes

Keywords

  • growth factor
  • promoter
  • retinoblastoma response element
  • tumor suppressor

Fingerprint Dive into the research topics of 'Regulation of transforming growth factor β1 gene expression by the product of the retinoblastoma-susceptibility gene'. Together they form a unique fingerprint.

Cite this