| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
The National Center for Infertility Research and the Reproductive Endocrine Sciences Center, Department of Medicine, Massachusetts General Hospital (C.K.W., W.F.C., A.L.S.), Boston, Massachusetts 02114; Department of Pathology and Laboratory Medicine, Women and Infants’ Hospital of Rhode Island (G.L-M.), Providence, Rhode Island 02905; and Department of Pathology, University of Southern California (W.Z.), Los Angeles, California 90033
Address all correspondence and requests for reprints to: Corrine K. Welt, Department of Medicine, The National Center for Infertility Research and the Reproductive Endocrine Sciences Center, Massachusetts General Hospital, Boston, Massachusetts 02114.
Activin induces proliferation in epithelial ovarian carcinoma cell lines, whereas follistatin (FS), an activin binding protein, inhibits this action. To test the hypothesis that activin production, in excess of inhibin and FS, results in cell proliferation in epithelial ovarian tumors, messenger RNA (mRNA) expression of the activin family of proteins, FS, and activin type I and II receptors was examined in 25 primary epithelial ovarian tumors and tumor epithelium in culture (n = 7) using RT-PCR. Activin A was measured in the serum of ovarian cancer patients, and activin A, total inhibin, and FS protein secretion was measured from primary epithelial tumors in vitro. The effect of activin and FS on cell proliferation was assessed by measuring [3H]thymidine incorporation. All results were compared with normal ovarian epithelium.
All epithelial ovarian tumors expressed mRNA for the 
, ßA, and
ßB subunits; FS 288 and 315; and the activin type IA, IB, II, and IIB
receptors. ßA mRNA expression, as assessed using semiquantitative
RT-PCR, was 3-fold greater in cultured tumor epithelium than in primary
tumors (band density 0.86 ± 0.17 vs. 0.28 ±
0.09; P < 0.01). In addition, ßA mRNA was
abundantly expressed in normal epithelium in culture (n = 2),
whereas only trace amounts were seen in 2/9 primary epithelial
samples.
Activin protein was secreted by 24/25 primary epithelial ovarian tumors (range 0.2–155.8 ng/mL). In contrast, total inhibin was secreted by only 2/25 (range 0.01–0.92 ng/mL), whereas free FS was not detectable in the medium of any tumor (<0.5 ng/mL). Treatment with activin or FS did not consistently affect cell growth. Measurement of serum activin A in a subset of subjects and in 27 additional subjects with epithelial ovarian carcinoma (n = 33) revealed preoperative activin A levels >3 SD above the mean for pre- and postmenopausal women in 13/33 (39%) subjects.
We conclude that in epithelial ovarian cancer: 1) ßA subunit mRNA is expressed, 2) activin protein is secreted more frequently than inhibin and in greater quantities than FS, 3) ßA subunit mRNA expression is greater in neoplastic and normal epithelium in culture than in the primary tissue, 4) the majority of tumors in culture do not respond to activin or FS treatment with proliferation, and 5) serum activin levels may reflect tumor secretion in some patients. Thus, activin A appears to be available as an autocrine/paracrine factor in epithelial ovarian tumors and may contribute to circulating levels, but its role in tumorigenesis has yet to be defined.
This article has been cited by other articles:
 |
|
 |
|
  J. E. Burdette, R. M. Oliver, V. Ulyanov, S. M. Kilen, K. E. Mayo, and T. K. Woodruff Ovarian Epithelial Inclusion Cysts in Chronically Superovulated CD1 and Smad2 Dominant-Negative Mice Endocrinology, August 1, 2007; 148(8): 3595 - 3604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xia, P. B. Yu, Y. Sidis, H. Beppu, K. D. Bloch, A. L. Schneyer, and H. Y. Lin Repulsive Guidance Molecule RGMa Alters Utilization of Bone Morphogenetic Protein (BMP) Type II Receptors by BMP2 and BMP4 J. Biol. Chem., June 22, 2007; 282(25): 18129 - 18140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Choi, A. S. T. Wong, H.-F. Huang, and P. C. K. Leung Gonadotropins and Ovarian Cancer Endocr. Rev., June 1, 2007; 28(4): 440 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C.K. Leung and J.-H. Choi Endocrine signaling in ovarian surface epithelium and cancer Hum. Reprod. Update, March 1, 2007; 13(2): 143 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Welt, A. E. Taylor, J. Fox, G. M. Messerlian, J. M. Adams, and A. L. Schneyer Follicular Arrest in Polycystic Ovary Syndrome Is Associated with Deficient Inhibin A and B Biosynthesis J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5582 - 5587. [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]
|
|
|
|
 |
|
 M. D. Steller, T. J. Shaw, B. C. Vanderhyden, and J.-F. Ethier Inhibin Resistance Is Associated with Aggressive Tumorigenicity of Ovarian Cancer Cells Mol. Cancer Res., January 1, 2005; 3(1): 50 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Cobellis, F. M. Reis, S. Luisi, S. Danero, L. Pirtoli, G. Scambia, and F. Petraglia High Concentrations of Activin A in the Peritoneal Fluid of Women With Epithelial Ovarian Cancer Reproductive Sciences, May 1, 2004; 11(4): 203 - 206. [Abstract] [PDF]
|
|
|
|
 |
|
 C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium Experimental Biology and Medicine, October 1, 2002; 227(9): 724 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. J. van der Meijden, D. S. Lapointe, M. X. Luong, D. Peric-Hupkes, B. Cho, J. L. Stein, A. J. van Wijnen, and G. S. Stein Gene Profiling of Cell Cycle Progression through S-Phase Reveals Sequential Expression of Genes Required for DNA Replication and Nucleosome Assembly Cancer Res., June 1, 2002; 62(11): 3233 - 3243. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
K.-C. Choi, S. K. Kang, C.-J. Tai, N. Auersperg, and P. C. K. Leung The Regulation of Apoptosis by Activin and Transforming Growth Factor-{beta} in Early Neoplastic and Tumorigenic Ovarian Surface Epithelium J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2125 - 2135. [Abstract] [Full Text]
|
|
|
|
|
|
N. Auersperg, A. S. T. Wong, K.-C. Choi, S. K. Kang, and P. C. K. Leung Ovarian Surface Epithelium: Biology, Endocrinology, and Pathology Endocr. Rev., April 1, 2001; 22(2): 255 - 288. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. M. Reis, A. Faletti, S. Luisi, G. Bifulco, S. Cauci, F. Quadrifoglio, J. Dor, and F. Petraglia High concentrations of inhibin A and inhibin B in ovarian serous cystadenoma: relationship with oestradiol and nitric oxide metabolites Mol. Hum. Reprod., December 1, 2000; 6(12): 1079 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Minegishi, T. Kameda, T. Hirakawa, K. Abe, M. Tano, and Y. Ibuki Expression of Gonadotropin and Activin Receptor Messenger Ribonucleic Acid in Human Ovarian Epithelial Neoplasms Clin. Cancer Res., July 1, 2000; 6(7): 2764 - 2770. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. L. Juengel, L. D. Quirke, D. J. Tisdall, P. Smith, N. L. Hudson, and K. P. McNatty Gene Expression in Abnormal Ovarian Structures of Ewes Homozygous for the Inverdale Prolificacy Gene Biol Reprod, June 1, 2000; 62(6): 1467 - 1478. [Abstract] [Full Text]
|
|
|
|
|
|
C. K. Welt, D. J. McNicholl, A. E. Taylor, and J. E. Hall Female Reproductive Aging Is Marked by Decreased Secretion of Dimeric Inhibin J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 105 - 111. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
