TRANSFORMING GROWTH-FACTOR BETA(1)-MEDIATED INDUCTION OF JUNB IS SELECTIVELY INHIBITED BY EXPRESSION OF AD.12-E1A

Transforming growth factor beta (TGF-beta), a multifunctional polypept ide growth factor, regulates the expression of many genes critical to cell cycle progression, such as members of the jun gene family which e ncode components of the transcription factor complex AP-1. The transfo rming proteins encoded by the early region 1A of adenovirus12 (Ad.12-E 1A) abrogate some of the cellular responses to TGF-beta as well as aff ecting, differentially, the expression of cellular jun genes. Our data demonstrate that expression of Ad.12-E1A in rat 3Y1 fibroblast cells inhibits induction of junB by TGF-beta(1) while not altering the regul ation of junB by phorbol ester or serum. Regulation of c-jun gene expr ession by TGF-beta(1), phorbol ester, and serum is not appreciably alt ered by the expression of Ad.l2-E1A. Inhibition of TGF-beta induced ju nB expression is not due to a defect in TGF-beta/receptor interaction on Ad.12-E1A transformed cells and is not observed in other isotypic f ibroblast cells transformed by SV40 or polyomavirus. These data sugges t that multiple, independent, intracellular signal transduction pathwa ys exist which mediate genomic responses to TGF-beta. Cellular express ion of Ad.12-E1A-12S gene products results in selective disruption of some TGF-beta(1) signaling cascades and not those activated by phorbol ester or serum. These data further suggest that some cellular targets which mediate TGF-beta(1) action may also be unique targets of action for the E1A-12S transforming protein of adenovirus12. (C) 1994 Wiley- Liss, Inc.