ADENOVIRUS E1A ANTAGONIZES BOTH NEGATIVE AND POSITIVE GROWTH SIGNALS ELICITED BY TRANSFORMING GROWTH-FACTOR-BETA-1

Transforming growth factor beta 1 (TGF beta 1) is a cytokine capable o f inhibiting or stimulating cell growth, depending on the nature of th e target cell. Inhibition of cell growth by TGF beta 1 is thought to b e mediated by TGF beta 1-induced changes in the expression and activit y of cell cycle regulatory proteins like cyclin-dependent kinase (cdk) 2 and cdk4. Here we show that adenovirus E1A blocks growth inhibition by TGF beta 1. The activity of cdk2 was strongly inhibited by TGF bet a 1 in control cells but not in E1A-expressing cells. Similarly, an ea rly event in TGF beta 1 signaling, junB induction, was significantly r educed in E1A-expressing cells. E1A also interferes with growth stimul ation of NRK cells by TGF beta 1, both in monolayer and in soft agar. In these cells, E1A also interferes with junB induction by TGF beta 1. Moreover, E1A abrogates TCF beta 1-induced production of an autocrine -acting platelet-derived growth factor-like activity. These results sh ow that E1A can interfere with TGF beta 1-induced growth-inhibiting as well as growth-promoting signals.