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Expression of Activin A and Follistatin Core Proteins by Human Prostate Tumor Cell Lines

Institute of Reproduction and Development (S.J.M., S.L.M., H.W., G.P.R.), 27–31 Wright St, Clayton, Victoria, Australia, 3168; Department of Biological and Molecular Sciences (L.W.E., N.P.G.), Oxford Brookes University, Headington, Oxford, OX3 0BP, United Kingdom

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

Activin and follistatin (FS) messenger RNA and protein are expressed and localized to human prostate tissue from men with high grade cancer and to human prostate tumor cell lines LNCaP, DU145, and PC3. Although activin A induces apoptosis and inhibits cell proliferation in LNCaP cells, PC3 cells are insensitive to the effect of exogenous addition of activin A. The results of this study show that activin A and FS are produced and can be measured by specific enzyme-linked immunosorbent assays in PC3 cells and media but are not detectable in LNCaP cells. Over 10 days in culture, the production of activin A by PC3 cells declines and is inversely correlated (r = -0.779) to FS288 production, which steadily increases and is significantly elevated compared with Day 1 of culture. The presence of FS288 and FS315 proteins was confirmed by immunocytochemistry and showed that only PC3 cells produced the FS288 isoform. Western blotting of PC3 cell media confirmed the presence of the FS288 isoform. Blockade of FS288 activity with a neutralizing antibody rendered PC3 cells responsive to activin A, as measured by inhibition of proliferation. Collectively, these results suggest that PC3 tumor cells are insensitive to activin A because they produce measurable amounts of activin ligand and FS288 protein, which is capable of blocking the autocrine response of these cells to activin A.

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