This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 Thomas, T. Z. Articles by Risbridger, G. P. Search for Related Content PubMed PubMed Citation Articles by Thomas, T. Z. Articles by Risbridger, G. P.

Expression and Localization of Activin Subunits and Follistatins in Tissues from Men with High Grade Prostate Cancer

Institute of Reproduction and Development, Monash University (T.Z.T., H.W., P.N., M.K.O., G.P.R.), Clayton; and Melbourne Pathology (J.P.), Collingwood, Australia; and Oxford Brookes University (L.W.E., N.P.G.), Headington, United Kingdom

Address all correspondence and requests for reprints to: Dr. G. P. Risbridger, Institute of Reproduction and Development, Monash University, Level 3, Block E, Monash Medical Center, 246 Clayton Road, Clayton 3168, Australia. E-mail: gail.risbridger{at}med.monash.edu.au

Activins are growth and differentiation factors that have growth inhibitory effects on LNCaP and DU145, but not PC3, human prostate tumor cell lines. Activin-binding proteins, follistatins, block the inhibitory actions of exogenously added activins on LNCaP and DU145 tumor cell lines. Based on these in vitro observations using human prostate tumor cell lines, the aims of this study were to determine whether activins and follistatins are expressed in the human prostate in tissues from men with high grade prostate cancer. The expression and cellular localization of these proteins in malignant and nonmalignant regions of these tissues were compared to determine whether any changes occur with progression to malignancy. The results demonstrate that activins and follistatins are synthesized in tissues from men with high grade prostate cancer, and that messenger ribonucleic acid (mRNA) and protein for the activin ß_A- and ß_B-subunits and follistatin is expressed and localized to poorly differentiated tumor cells. In the nonmalignant regions, activin ß_A and ß_B subunit mRNA and proteins are predominantly localized to the epithelium. Follistatin mRNA was expressed in the basal epithelial cells and in the fibroblastic stroma; however, the localization of follistatin proteins using two specific antisera demonstrated a difference between the follistatin isoforms expressed in basal cells and the stroma. In the progression to malignancy, the colocalization of follistatin and activins to the tumor cells in vivo implies that resistance to the growth inhibitory effects of activin may be conferred by follistatins.

This article has been cited by other articles:

				A. L. Blount, K. Schmidt, N. J. Justice, W. W. Vale, W. H. Fischer, and L. M. Bilezikjian FoxL2 and Smad3 Coordinately Regulate Follistatin Gene Transcription J. Biol. Chem., March 20, 2009; 284(12): 7631 - 7645. [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]

				K. Yoshinaga, H. Inoue, T. Utsunomiya, H. Sonoda, T. Masuda, K. Mimori, Y. Tanaka, and M. Mori N-Cadherin Is Regulated by Activin A and Associated with Tumor Aggressiveness in Esophageal Carcinoma Clin. Cancer Res., September 1, 2004; 10(17): 5702 - 5707. [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]

				P. Harkonen, S. Torn, R. Kurkela, K. Porvari, A. Pulkka, A. Lindfors, V. Isomaa, and P. Vihko Sex Hormone Metabolism in Prostate Cancer Cells during Transition to an Androgen-Independent State J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 705 - 712. [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]

				Y.-G. Chen, H. M. Lui, S.-L. Lin, J. M. Lee, and S.-Y. Ying Regulation of Cell Proliferation, Apoptosis, and Carcinogenesis by Activin Experimental Biology and Medicine, February 1, 2002; 227(2): 75 - 87. [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]

				S Wildi, J Kleeff, H Maruyama, C A Maurer, M W Buchler, and M Korc Overexpression of activin A in stage IV colorectal cancer Gut, September 1, 2001; 49(3): 409 - 417. [Abstract] [Full Text] [PDF]

				S. L. Mellor, M. Cranfield, R. Ries, J. Pedersen, B. Cancilla, D. de Kretser, N. P. Groome, A. J. Mason, and G. P. Risbridger Localization of Activin {beta}A-, {beta}B-, and {beta}C-Subunits in Human Prostate and Evidence for Formation of New Activin Heterodimers of {beta}C-Subunit J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4851 - 4858. [Abstract] [Full Text]

				S. J. McPherson, S. L. Mellor, H. Wang, L. W. Evans, N. P. Groome, and G. P. Risbridger Expression of Activin A and Follistatin Core Proteins by Human Prostate Tumor Cell Lines Endocrinology, November 1, 1999; 140(11): 5303 - 5309. [Abstract] [Full Text]

				C. C. Sprenger, S. E. Damon, V. Hwa, R. G. Rosenfeld, and S. R. Plymate Insulin-like Growth Factor Binding Protein-related Protein 1 (IGFBP-rP1) Is a Potential Tumor Suppressor Protein for Prostate Cancer Cancer Res., May 1, 1999; 59(10): 2370 - 2375. [Abstract] [Full Text] [PDF]

				R. A. Jarred, B. Cancilla, M. Richards, N. P. Groome, K. P. McNatty, and G. P. Risbridger Differential Localization of Inhibin Subunit Proteins in the Ovine Testis during Fetal Gonadal Development Endocrinology, February 1, 1999; 140(2): 979 - 986. [Abstract] [Full Text]

				F. Petraglia, P. Florio, S. Luisi, R. Gallo, A. Gadducci, P. Viganò, A. M. Di Blasio, A. R. Genazzani, and W. Vale Expression and Secretion of Inhibin and Activin in Normal and Neoplastic Uterine Tissues. High Levels of Serum Activin A in Women with Endometrial and Cervical Carcinoma J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1194 - 1200. [Abstract] [Full Text]

				S. L. Mellor, M. G. Richards, J. S. Pedersen, D. M. Robertson, and G. P. Risbridger Loss of the Expression and Localization of Inhibin {alpha}-Subunit in High Grade Prostate Cancer J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 969 - 975. [Abstract] [Full Text]