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. We overexpressed truncated type II activin and/or TGF-beta 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-beta receptor (AML-tTR cells), the inhibitory effect of TGF-beta 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-beta 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.
Zhang
Y Q
YQ
Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Mashima
H
H
Kanzaki
M
M
Shibata
H
H
Kojima
I
I
D029404:Activin Receptors; D028341:Activins; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D018076:DNA, Complementary / Q000235:genetics; D007265:Inhibins / Q000502:physiology*; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000502:physiology*
D018076:DNA, Complementary; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D004247:DNA; D029404:Activin Receptors