Activin βC-subunit heterodimers provide a new mechanism of regulating activin levels in the prostate

Sally L. Mellor, Emma M A Ball, Anne E. O'Connor, Jean François Ethier, Mark Cranfield, Jacqueline F. Schmitt, David J. Phillips, Nigel P. Groome, Gail P. Risbridger

Research output: Contribution to journalArticleResearchpeer-review

53 Citations (Scopus)


Activins are formed by dimerization of β-subunits and, as members of the TGF-β superfamily, have diverse roles as potent growth and differentiation factors. As the biological function of the activin C homodimer (βCC) is unknown, we sought to compare activin A (βAA), B (βBB), and C homodimer bioactivities and to investigate the consequences of activin βC-subunit overexpression in prostate tumor cells. Exogenous activin A and B homodimers inhibited cell growth and activated activin-responsive promoters. In contrast, the activin C homodimer was unable to elicit these responses. We previously showed that the activin βC-subunit heterodimerized with activin βA in vitro to form activin AC. Therefore, we hypothesize that the activin β C-subunit regulates the levels of bioactive activin A by the formation of activin AC heterodimers. To test this hypothesis, we measured activin AC heterodimer production using a novel specific two-site ELISA that we developed for this purpose. In the PC3 human prostate tumor cell line, activin βC-subunit overexpression increased activin AC heterodimer levels, concomitantly reduced activin A levels, and decreased activin signaling. Overall, these data are consistent with a role for the activin β C-subunit as a regulatory mechanism to reduce activin A secretion via intracellular heterodimerization.

Original languageEnglish
Pages (from-to)4410-4419
Number of pages10
Issue number10
Publication statusPublished - 1 Oct 2003

Cite this