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Assessment of the role of activin A and transforming growth factor β in the regulation of AML12 cell growth
Author(s) -
Zhang Y,
Mashima H,
Kanzaki M,
Shibata H,
Kojima I
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510250612
Subject(s) - autocrine signalling , activin type 2 receptors , transforming growth factor , microbiology and biotechnology , biology , epidermal growth factor , acvr2b , dna synthesis , growth factor , receptor , activin receptor , medicine , cancer research , tgf beta signaling pathway , dna , biochemistry
The present study was conducted to determine the role of two autocrine factors, activin A and transforming growth factor β (TGF‐β), in the growth regulation of AML12 hepatocytes. We overexpressed truncated type II activin and/or TGF‐β receptors in AML12 cells. In AML12 cells 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 in the presence and absence of epidermal growth factor (EGF). However, AML‐tAR cells could not grow in soft agar. Follistatin augmented EGF‐induced DNA synthesis in AML12 cells, whereas it was ineffective in AML‐tAR cells. In AML12 cells overexpressing truncated type II TGF‐β receptor (AML‐tTR cells), the inhibitory effect of TGF‐β on DNA synthesis was blocked. AML‐tTR cells proliferated faster than parental cells, both in the presence and absence of EGF, but at a slower rate than 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 in soft agar. These results indicate that both activin A and TGF‐β act as autocrine inhibitors of DNA synthesis in AML12 cells, and that the blocking of the actions of two factors does not lead to transformation. Activin A is a predominant autocrine factor in these cells.