Localization of activin beta(A)-, beta(B)-, and beta(C)-subunits in humanprostate and evidence for formation of new activin heterodimers of beta(C)-subunit.
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 alpha-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.
Mellor
S L
SL
Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia.
Cranfield
M
M
Ries
R
R
Pedersen
J
J
Cancilla
B
B
de Kretser
D
D
Groome
N P
NP
Mason
A J
AJ
Risbridger
G P
GP
D028341:Activins; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D015153:Blotting, Western; D002454:Cell Differentiation; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D028322:Inhibin-beta Subunits; D007265:Inhibins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000033:anatomy & histology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007202:Indicators and Reagents; D010455:Peptides; C044147:activin B; C103008:inhibin beta A subunit; D028341:Activins; D007265:Inhibins; D028322:Inhibin-beta Subunits; D013936:Thymidine