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 Di Simone, N. Articles by Schneyer, A. L. Search for Related Content PubMed PubMed Citation Articles by Di Simone, N. Articles by Schneyer, A. L. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Testicular Cancer Testicular Disorders

Activin Regulates ßA-Subunit and Activin Receptor Messenger Ribonucleic Acid and Cellular Proliferation in Activin-Responsive Testicular Tumor Cells¹

Reproductive Endocrine Unit and National Center for Infertility Research, Massachusetts General Hospital, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Alan Schneyer, Ph.D., Reproductive Endocrine Unit, BHX-5, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: schneyer.alan{at}mgh.harvard.edu

Activin, a member of the transforming growth factor-ß superfamily of growth and differentiation factors, has a number of actions in embryonic as well as adult tissues. These actions are mediated via a family of receptors containing two subtypes and at least two members of each subtype. Recent evidence demonstrates that activin-responsive cell lines containing different subsets of these receptors are valuable models for dissecting functional relationships among receptor subtype, signal transduced, and response obtained.

TT cells, derived from a p53^-/-/-inhibin^-/- mouse testicular tumor, respond to activin by proliferating, a response that can be inhibited by follistatin (FS) treatment. Using semiquantitative RT-PCR methods, we characterized steady state messenger RNA (mRNA) levels for the inhibin/activin subunits, FS, and activin receptor subtypes under basal conditions and in the presence of activin or FS. These cells produced ample immunoreactive activin A and FS, necessitating higher treatment doses to observe any modulation of cellular proliferation. Furthermore, in the presence of exogenous activin, mRNA levels for activin receptor type IIA (ACTRIIA) and ßA were significantly and profoundly suppressed. In addition, both ACTR1B and ACTRIIB were detectable and down-regulated by exogenous activin, although not to the degree observed for ACTRIIA and ßA. Finally, activin treatment at the higher doses, which decreased activin receptor mRNA levels, resulted in inhibition of cellular proliferation. Taken together with previous observations, our results support the model that these tumor cells respond to an autocrine activin signal by proliferating, whereas exogenous or excess activin results in down-regulation of activin receptor and activin biosynthesis, suggesting a potential autocrine/paracrine mechanism by which activin can modulate its own signal.

This article has been cited by other articles:

				Y. Sidis, A. Mukherjee, H. Keutmann, A. Delbaere, M. Sadatsuki, and A. Schneyer Biological Activity of Follistatin Isoforms and Follistatin-Like-3 Is Dependent on Differential Cell Surface Binding and Specificity for Activin, Myostatin, and Bone Morphogenetic Proteins Endocrinology, July 1, 2006; 147(7): 3586 - 3597. [Abstract] [Full Text] [PDF]

				D. Peters, J. Freund, and R. L. Ochs Genome-wide transcriptional analysis of carboplatin response in chemosensitive and chemoresistant ovarian cancer cells Mol. Cancer Ther., October 1, 2005; 4(10): 1605 - 1616. [Abstract] [Full Text] [PDF]

				K. Kwong, R. A. Vaishnav, Y. Liu, N. Subhedar, A. J. Stromberg, M. L. Getchell, and T. V. Getchell Target ablation-induced regulation of macrophage recruitment into the olfactory epithelium of Mip-1{alpha}-/- mice and restoration of function by exogenous MIP-1{alpha} Physiol Genomics, December 15, 2004; 20(1): 73 - 86. [Abstract] [Full Text] [PDF]

				K. D. Carpenter, K. Hayashi, and T. E. Spencer Ovarian Regulation of Endometrial Gland Morphogenesis and Activin-Follistatin System in the Neonatal Ovine Uterus Biol Reprod, September 1, 2003; 69(3): 851 - 860. [Abstract] [Full Text] [PDF]

				T. Fujiwara, Y. Sidis, C. Welt, G. Lambert-Messerlian, J. Fox, A. Taylor, and A. Schneyer Dynamics of Inhibin Subunit and Follistatin mRNA during Development of Normal and Polycystic Ovary Syndrome Follicles J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4206 - 4215. [Abstract] [Full Text] [PDF]

				A. Delbaere, Y. Sidis, and A. L. Schneyer Differential Response to Exogenous and Endogenous Activin in a Human Ovarian Teratocarcinoma-Derived Cell Line (PA-1): Regulation by Cell Surface Follistatin Endocrinology, June 1, 1999; 140(6): 2463 - 2470. [Abstract] [Full Text]

				Y. Sidis,, T. Fujiwara,, L. Leykin,, K. Isaacson,, T. Toth,, and A. L. Schneyer Characterization of Inhibin/Activin Subunit, Activin Receptor, and Follistatin Messenger Ribonucleic Acid in Human and Mouse Oocytes: Evidence for Activin's Paracrine Signaling from Granulosa Cells to Oocytes Biol Reprod, October 1, 1998; 59(4): 807 - 812. [Abstract] [Full Text]