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This Article Full Text Full Text (PDF) All Versions of this Article: 287/2/E247    most recent 00390.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Wada, W. Articles by Kojima, I. Search for Related Content PubMed PubMed Citation Articles by Wada, W. Articles by Kojima, I.

Assessment of the function of the _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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