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Localization of Activin ß_A-, ß_B-, and ß_C-Subunits in Human Prostate and Evidence for Formation of New Activin Heterodimers of ß_C-Subunit¹

Monash Institute of Reproduction and Development (S.L.M., B.C., D.d.K., G.P.R.), Monash University, Melbourne, Victoria, Australia; School of Biological and Molecular Sciences, Oxford Brookes University (M.C., N.P.G.), Headington, Oxford, United Kingdom; BIOPHARM (R.R.), Heidelberg, Germany; Melbourne Pathology, Collingwood, Victoria, Australia (J.P.); and Department of Microbiology, Monash University (A.J.M.), Clayton, Victoria, Australia

Address all correspondence and requests for reprints to: Dr. Gail P. Risbridger, Monash Institute of Reproduction and Development, 27–31 Wright Street, Clayton 3168, Victoria, Australia. E-mail: gail.risbridger{at}med.monash.edu.au

Activin ligands are formed by dimerization of activin ß_A- and/or ß_B-subunits to produce activins A, AB, or B. These ligands are members of the transforming growth factor-ß superfamily and act as growth and differentiation factors in many cells and tissues. New additions to this family include activin ß_C-, ß_D-, and ß_E-subunits. The aim of this investigation was to examine the localization of and dimerization among activin subunits; the results demonstrate that activin ß_C can form dimers with activin ß_A and ß_B in vitro, but not with the inhibin -subunit. Using a specific antibody, activin ß_C protein was localized to human liver and prostate and colocalized with ß_A- and ß_B-subunits to specific cell types in benign and malignant prostate tissues. Activin C did not alter DNA synthesis of the prostate tumor cell line, LNCaP, or the liver tumor cell line, HepG2, in vitro when added alone or with activin A. Therefore, the capacity to form novel activin heterodimers (but not inhibin C) resides in the human liver and prostate. Activin A, AB, and B have diverse actions in many tissues, including liver and prostate, but there is no known biological activity for activin C. Thus, the evidence of formation of activin AC or BC heterodimers may have significant implications in the regulation of levels and/or biological activity of other activins in these tissues.

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