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

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.