This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jeruss, J. S. Articles by Woodruff, T. K. Search for Related Content PubMed PubMed Citation Articles by Jeruss, J. S. Articles by Woodruff, T. K.

Down-Regulation of Activin, Activin Receptors, and Smads in High-Grade Breast Cancer¹

Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208 [J. S. J., T. K. W.]; Departments of Surgery [J. S. J.], Pathology [C. D. S.], Preventative Medicine [A. W. R.], and Medicine [T. K. W.], Feinberg School of Medicine, and Robert H. Lurie Comprehensive Cancer Center [T. K. W.], Northwestern University, Chicago, Illinois; and Department of Pathology, Evanston Northwestern Healthcare, Evanston, Illinois [C. D. S.]

Activin and transforming growth factor (TGF)-ß, members of the TGF-ß superfamily of growth factors, have been implicated in both mammary gland development and breast carcinogenesis. TGF-ß is thought to be involved in the maintenance of mammary gland ductal architecture and postlactational involution. TGF-ß acts as both a tumor suppressor and has oncogenic capacities in breast cancer tissue. Activin is associated with growth modulation in glandular organs, and its receptors and signaling proteins are present and regulated during postnatal mammary gland development, primarily during the lactational phase. The presence of the major components of the activin signal transduction pathway in different pathologic grades of breast cancer tissue has not been described thoroughly, despite evidence from in vitro studies suggesting that activin can inhibit proliferation in breast cancer-derived cells. On the basis of the growth regulatory capacity of activin, we hypothesized that the components of this signal transduction system would be deregulated as breast cancer becomes more aggressive. To test this hypothesis, breast cancer samples were substratified by pathologic grade, a known prognostic marker for breast cancer, and then examined for the presence and cellular localization of activin ligand subunits (ßA- and ßB-), receptors (Act RIIA, Act RIIB, and Act RIB), and signaling proteins, Smads 2, 3, and 4, by immunohistochemistry and immunofluorescent analysis. Breast tissue from healthy patients undergoing reduction mammoplasty was also studied. The activin ßA-subunit was present in all of the tissues examined, whereas the ßB-subunit, activin type II receptors, and Smads were less evident in high-grade cancers. Significant correlations were made in breast cancer specimens between a decrease in nuclear Smad 3 abundance and high tumor grade, high architectural grade, larger tumor size, and hormone receptor negativity. Thus, activin signal transduction components are present in normal tissue and grade 1 cancer but down-regulated in high-grade cancer. The deregulation of this signal transduction system may be relevant to advancing oncogenic progression.

This article has been cited by other articles:

				J. E Burdette and T. K Woodruff Activin and estrogen crosstalk regulates transcription in human breast cancer cells Endocr. Relat. Cancer, September 1, 2007; 14(3): 679 - 689. [Abstract] [Full Text] [PDF]

				D. Razanajaona, S. Joguet, A.-S. Ay, I. Treilleux, S. Goddard-Leon, L. Bartholin, and R. Rimokh Silencing of FLRG, an Antagonist of Activin, Inhibits Human Breast Tumor Cell Growth Cancer Res., August 1, 2007; 67(15): 7223 - 7229. [Abstract] [Full Text] [PDF]

				M. C. Banas, W. T. Parks, K. L. Hudkins, B. Banas, M. Holdren, M. Iyoda, T. A. Wietecha, J. Kowalewska, G. Liu, and C. E. Alpers Localization of TGF-{beta} Signaling Intermediates Smad2, 3, 4, and 7 in Developing and Mature Human and Mouse Kidney J. Histochem. Cytochem., March 1, 2007; 55(3): 275 - 285. [Abstract] [Full Text] [PDF]

				J. E. Burdette, J. S. Jeruss, S. J. Kurley, E. J. Lee, and T. K. Woodruff Activin A Mediates Growth Inhibition and Cell Cycle Arrest through Smads in Human Breast Cancer Cells Cancer Res., September 1, 2005; 65(17): 7968 - 7975. [Abstract] [Full Text] [PDF]

				A. Shin, X.-O. Shu, Q. Cai, Y.-T. Gao, and W. Zheng Genetic Polymorphisms of the Transforming Growth Factor-{beta}1 Gene and Breast Cancer Risk: A Possible Dual Role at Different Cancer Stages Cancer Epidemiol. Biomarkers Prev., June 1, 2005; 14(6): 1567 - 1570. [Abstract] [Full Text] [PDF]