This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McPherson, S. J. Articles by Risbridger, G. P. Search for Related Content PubMed PubMed Citation Articles by McPherson, S. J. Articles by Risbridger, G. P.

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.

This article has been cited by other articles:

				E. Gold, N. Jetly, M. K. O'Bryan, S. Meachem, D. Srinivasan, S. Behuria, L. G. Sanchez-Partida, T. Woodruff, S. Hedwards, H. Wang, et al. Activin C Antagonizes Activin A in Vitro and Overexpression Leads to Pathologies in Vivo Am. J. Pathol., January 1, 2009; 174(1): 184 - 195. [Abstract] [Full Text] [PDF]

				B. M. Necela, W. Su, and E. A. Thompson Peroxisome Proliferator-activated Receptor {gamma} Down-regulates Follistatin in Intestinal Epithelial Cells through SP1 J. Biol. Chem., October 31, 2008; 283(44): 29784 - 29794. [Abstract] [Full Text] [PDF]

				A. Pellagatti, M. Jadersten, A.-M. Forsblom, H. Cattan, B. Christensson, E. K. Emanuelsson, M. Merup, L. Nilsson, J. Samuelsson, B. Sander, et al. Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q- syndrome patients PNAS, July 3, 2007; 104(27): 11406 - 11411. [Abstract] [Full Text] [PDF]

				Y.-G. Chen, Q. Wang, S.-L. Lin, C. D. Chang, J. Chung, and S.-Y. Ying Activin Signaling and Its Role in Regulation of Cell Proliferation, Apoptosis, and Carcinogenesis. Experimental Biology and Medicine, May 1, 2006; 231(5): 534 - 544. [Abstract] [Full Text] [PDF]

				S. Patella, D. J. Phillips, J. Tchongue, D. M. de Kretser, and W. Sievert Follistatin attenuates early liver fibrosis: effects on hepatic stellate cell activation and hepatocyte apoptosis Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G137 - G144. [Abstract] [Full Text] [PDF]

				G. Chen, M. Nomura, H. Morinaga, E. Matsubara, T. Okabe, K. Goto, T. Yanase, H. Zheng, J. Lu, and H. Nawata Modulation of Androgen Receptor Transactivation by FoxH1: A NEWLY IDENTIFIED ANDROGEN RECEPTOR COREPRESSOR J. Biol. Chem., October 28, 2005; 280(43): 36355 - 36363. [Abstract] [Full Text] [PDF]

				J. L. Carey, L. M. Sasur, H. Kawakubo, V. Gupta, B. Christian, P. M. Bailey, and S. Maheswaran Mutually Antagonistic Effects of Androgen and Activin in the Regulation of Prostate Cancer Cell Growth Mol. Endocrinol., March 1, 2004; 18(3): 696 - 707. [Abstract] [Full Text] [PDF]

				S. L. Mellor, E. M. A. Ball, A. E. O'Connor, J.-F. Ethier, M. Cranfield, J. F. Schmitt, D. J. Phillips, N. P. Groome, and G. P. Risbridger Activin {beta}C-Subunit Heterodimers Provide a New Mechanism of Regulating Activin Levels in the Prostate Endocrinology, October 1, 2003; 144(10): 4410 - 4419. [Abstract] [Full Text] [PDF]

				F. M. Reis, L. Cobellis, L. C. Tameirao, G. Anania, S. Luisi, I. S. B. Silva, W. Gioffre, A. M. di Blasio, and F. Petraglia Serum and Tissue Expression of Activin A in Postmenopausal Women with Breast Cancer J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2277 - 2282. [Abstract] [Full Text] [PDF]

				G. P. Risbridger, J. F. Schmitt, and D. M. Robertson Activins and Inhibins in Endocrine and Other Tumors Endocr. Rev., December 1, 2001; 22(6): 836 - 858. [Abstract] [Full Text] [PDF]

				J. Massagué and Y.-G. Chen Controlling TGF-beta signaling Genes & Dev., March 15, 2000; 14(6): 627 - 644. [Full Text]

				D. C. Danila, W. J. Inder, X. Zhang, J. M. Alexander, B. Swearingen, E. T. Hedley-Whyte, and A. Klibanski Activin Effects on Neoplastic Proliferation of Human Pituitary Tumors J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1009 - 1015. [Abstract] [Full Text]