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Serum and Tissue Expression of Activin A in Postmenopausal Women with Breast Cancer

Chair of Obstetrics and Gynecology (F.M.R., L.C., S.L., W.G., F.P.), University of Siena, 53100 Siena, Italy; Department of Obstetrics and Gynecology, UFMG (F.M.R.) and Hospital Maternidade Odete Valadares (L.C.T.), 30130-100 Belo Horizonte, Brazil; Department of Surgery (G.A.), University of Ferrara, 44100 Ferrara, Italy; Department of Physiology (I.S.B.S.), UFRGS, 90050-170 Porto Alegre, Brazil; and Laboratory of Molecular Biology (A.M.d.B.), Istituto Auxologico Italiano, 20135 Milan, Italy

Address all correspondence and requests for reprints to: Felice Petraglia, M.D., Chair of Obstetrics and Gynecology, University of Siena, Policlinico Le Scotte, Viale Bracci, 53100 Siena, Italy. E-mail: . petraglia{at}unisi.it

Abstract

Activins are growth factors involved in the control of cell proliferation and differentiation. Human breast tissues express immunoreactive activin subunits, and activin A is able to inhibit the replication of mammary cells in vitro. The aim of the present study was to evaluate 1) whether breast cancer expresses activin ßA subunit mRNA, 2) whether serum activin A levels are altered in postmenopausal women with breast cancer, and 3) how circulating activin A levels change after tumor removal. Four groups of women (n = 158) were enrolled for the present prospective study: two groups were composed of postmenopausal women with breast cancer (n = 74) or benign lesions (n = 15); the third was a control group composed of healthy postmenopausal women (n = 62); and the fourth group included healthy fertile women (n = 7) undergoing plastic surgery with removal of non-neoplastic mammary tissue.

RT-PCR showed that ßA subunit mRNA was expressed in breast carcinoma, fibroadenoma, and normal mammary tissue, and the level of expression was higher in carcinoma than in normal tissue (P < 0.05). Dimeric activin A was detectable in homogenates of breast cancer tissue at concentrations twice as high as in non-neoplastic tissue (P < 0.01). In women with breast cancer, median serum activin A levels were significantly higher than in controls (P < 0.001). The high serum activin A levels in patients with breast cancer were not correlated with the presence of lymph node metastasis, tumor grade, or tumor diameter. After tumor excision, a significant decrease of activin A in the first and second postoperative days was observed (P < 0.01; Friedman’s ANOVA). Conversely, activin A levels remained unchanged after plastic surgery in healthy women. The present results suggest that activin A is expressed and secreted in postmenopausal women with breast cancer. The pathophysiological and possible clinical implications of this finding remain to be investigated.

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