Localization of activin ßA-, ßB-, and ßC-subunits in human prostate and evidence for formation of new activin heterodimers of ßC-subunit

Activin ligands are formed by dimerization of activin beta (A)- and/or beta (B)-subunits to produce activins A, AB, or B. These ligands are members of the transforming growth factor-beta superfamily and act as growth and differentiation factors in many cells and tissues. New additions to this family include activin beta (C)-, beta (D)- and beta (E)-subunits. The aim of this investigation was to examine the localization of and dimerization among activin subunits; the results demonstrate that activin beta (C) can form dimers with activin beta (A) and beta (B) in vitro, but not with the inhibin alpha -subunit. Using a specific antibody, activin beta (C) protein was localized to human liver and prostate and colocalized with beta (A)- and beta (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.