CONTROL OF JUNB AND EXTRACELLULAR-MATRIX PROTEIN EXPRESSION BY TRANSFORMING GROWTH FACTOR-BETA-1 IS INDEPENDENT OF SIMIAN VIRUS-40 T-ANTIGEN-SENSITIVE GROWTH-INHIBITORY EVENTS

Treatment of Mv1Lu mink lung epithelial cells with transforming growth factor-beta-1 (TGF-beta-1) prevents phosphorylation of the retinoblastoma susceptibility gene product, RB, in late G1 phase of the cell cycle, which is thought to retain RB in a growth-suppressive state. This effect is paralleled by cell cycle arrest in late G1 (M. Laiho, J. A. DeCaprio, J. W. Ludlow, D. M. Livingston, and J. Massague, Cell 62:175-185, 1990). Arrest can be prevented by expression of simian virus 40 T antigen, which binds to underphosphorylated RB, presumably blocking its growth-suppressive activity. The response of cells to TGF-beta-1, however, is complex and includes changes in the levels of expression of genes encoding nuclear transcription factors and extracellular matrix components. To define the relationships among various components of the TGF-beta-1 response, we have investigated the effect of TGF-beta-1 on cells whose growth-inhibitory response to this factor is prevented by T antigen. TGF-beta-1 addition to exponentially growing Mv1Lu cells increased the levels of junB mRNA and of three extracellular matrix proteins: plasminogen activator inhibitor-1, fibronectin, and thrombospondin. Kinetically, the effects on junB and plasminogen activator inhibitor-1 expression occurred faster (half-maximal at 1 to 2 h) than the effects on fibronectin and thrombospondin expression (half-maximal at 6 to 10 h). These effects either preceded or overlapped, respectively, the withdrawal of Mv1Lu cells from the cell cycle. Expression of a transfected T-antigen gene in Mv1Lu cells, however, did not prevent any of these responses to TGF-beta-1. The results indicate that TGF-beta-1-stimulated expression of junB and extracellular matrix proteins in Mv1Lu cells can occur independently of the T-antigen-sensitive events that lead to growth arrest.