ASSESSMENT OF THE ROLE OF ACTIVIN-A AND TRANSFORMING-GROWTH-FACTOR-BETA IN THE REGULATION OF AML12 CELL-GROWTH

The present study was conducted to determine the role of two autocrine factors, activin A and transforming growth factor beta (TGF-beta), in the growth regulation of AML12 hepatocytes, me overexpressed truncate d type II activin and/or TGF-beta receptors in AML12 cells, In AML12 c ells overexpressing truncated type II activin receptors (AML-tAR cells ), the inhibitory effect of activin A on DNA synthesis was completely blocked, AML-tAR cells proliferated faster than parental cells, both i n the presence and absence of epidermal growth factor (EGF). However, AML-tAR cells could not grow in soft agar. Fol listatin augmented EGF- induced DNA synthesis in AML12 cells, whereas it was ineffective in AM L-tAR cells, In AML12 cells overexpressing truncated type II TGF-beta receptor (AML-tTR cells), the inhibitory effect of TGF-beta on DNA syn thesis was blocked. AML-tTR cells proliferated faster than parental ce lls, both in the presence and absence of EGF, but at a slower rate tha n that of AML-tAR cells, AML-tTR cells did not grow in soft agar. The growth rate of cells overexpressing both types of truncated receptors was identical to that of AML-tAR cells, and these cells did not grow i n soft agar, These results indicate that both activin A and TGF-beta a ct as autocrine inhibitors of DNA synthesis in AML12 cells, and that t he blocking of the actions of two factors does not lead to transformat ion. Activin A is a predominant autocrine factor in these cells.