| First Author | Herrera RE | Year | 1996 |
| Journal | Mol Biol Cell | Volume | 7 |
| Issue | 9 | Pages | 1335-42 |
| PubMed ID | 8885230 | Mgi Jnum | J:35415 |
| Mgi Id | MGI:82864 | Doi | 10.1091/mbc.7.9.1335 |
| Citation | Herrera RE, et al. (1996) TGF beta-induced growth inhibition in primary fibroblasts requires the retinoblastoma protein. Mol Biol Cell 7(9):1335-42 |
| abstractText | Transforming growth factor beta (TGF beta) inhibits cell proliferation by inducing a G1 cell-cycle arrest. Cyclin/CDK complexes have been implicated in this arrest, because TGF beta treatment leads to inhibition of cyclin/CDK activity. We have investigated the role of the retinoblastoma protein (pRb) in TGF beta-induced growth arrest by using RB+/+ and RB-/- primary mouse embryo fibroblasts. In both of these cell types, TGF beta inhibits CDK4-associated kinase activity. However, whereas CDK2-associated kinase activity was completely inhibited by TGF beta in the wild-type cells, it was reduced only slightly in the RB mutant cells. In addition, at high-cell density the growth-inhibitory effects of TGF beta are no longer observed in the RB-/- cells; on the contrary, TGF beta treatment promotes the growth of these mutant fibroblasts. Thus, under certain cellular growth conditions, elimination of pRb transforms the growth-inhibitory effects of TGF beta into growth-stimulatory effects. These observations could help to explain why TGF beta is often found to enhance tumorigenicity in vivo and why inactivation of the RB gene leads to tumorigenesis. |
