TY - JOUR
T1 - Assessment of the role of activin A and transforming growth factor β in the regulation of AML12 cell growth
AU - Zhang, You Qing
AU - Mashima, Hirosato
AU - Kanzaki, Makoto
AU - Shibata, Hiroshi
AU - Kojima, Itaru
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1997
Y1 - 1997
N2 - 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 H 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.
AB - 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 H 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.
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U2 - 10.1002/hep.510250612
DO - 10.1002/hep.510250612
M3 - Article
C2 - 9185755
AN - SCOPUS:0030906357
VL - 25
SP - 1370
EP - 1375
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 6
ER -