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C-subunit of activin in cultured hepatocytes
1Institute for Molecular and Cellular Regulation, Gunma University and 2Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi 371-8512; and 3School of Veterinary Medicine and Animal Science, Kitasato University, Towada 034-8628, Japan
Submitted 28 August 2003 ; accepted in final form 12 December 2003
We assessed the function of the
C-subunit of activin in hepatocytes. We studied the effect of conditioned medium of Chinese hamster ovary (CHO) cell line stably expressing the
C gene (CHO-
C) on growth of AML12 hepatocytes. We also examined the effect of recombinant activin C and transfection of the
C gene by using adenovirus vector. CHO-
C secreted activin C, a homodimer of the
C, as well as precursors of the
C. The conditioned medium of CHO-
C increased both [3H]thymidine incorporation and the cell number in AML12 cells. It also supported survival of AML12 cells in a serum-free condition. Recombinant human activin C also increased both [3H]thymidine incorporation and the number of AML12 cells. Transfection of AML12 cells with the
C-subunit led to the stimulation of [3H]thymidine incorporation. Analysis of the conditioned medium revealed that the
C-subunit formed a heterodimer with the endogenous
A, the formation of which was dependent on the amount of
C expressed. Recombinant activin C did not affect the binding of 125I-activin A to its receptor or follistatin. These results indicate that activin C stimulates growth of AML12 cells. The
C-subunit modifies the function of the
A-subunit by multiple mechanisms.
activin C; growth; apoptosis
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