This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart 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 Okubo, T. Articles by Chen, S. Search for Related Content PubMed PubMed Citation Articles by Okubo, T. Articles by Chen, S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB 12-O-TETRADECANOYLPHORBOL-13-ACETATE DEXAMETHASONE

Regulation of Aromatase Expression in Human Ovarian Surface Epithelial Cells¹

Division of Immunology (T.O., S.C.), Beckman Research Institute of the City of Hope, Duarte, California 91010; and Laboratory of Gynecology Oncology, Department of Obstetrics, Gynecology and Reproductive Biology (S.C.M.), Brigham and Women’s Hospital, Harvard Medical School. Boston, Massachusetts 02115

Address correspondence and requests for reprints to: Dr. Shiuan Chen, Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010. E-mail: schen{at}coh.org

Ovarian cancer originates mainly from surface epithelial cells, which are potential targets of estrogen action. Using immunohistochemistry and RT-PCR analysis, aromatase (estrogen synthetase) can be detected in human ovarian surface epithelial tumors. In this study, we functionally characterized the aromatase expressed in a primary cell culture, normal human ovarian surface epithelial (HOSE) 17. The apparent K_m and V_max values were determined to be 5.8 ± 0.5 nM, and 0.3 ± 0.0 pmol/mg·h, respectively. The aromatase activity in HOSE 17 cells can be induced effectively by phorbol esters and forskolin, suggesting that estrogen biosynthesis in HOSE 17 cells is mainly regulated through protein kinase C- and protein kinase A-mediated mechanisms. Exon I-specific RT-PCR revealed that phorbol esters predominantly up-regulated promoter II. Whereas forskolin treatment increased exon I.3A-containing messenger RNA, the aromatase activity remained low in the cells treated with this agent. In vitro transcription/translation analysis using plasmids containing T7 promoter and the human snail gene (SnaH) as a reporter capped with different untranslated exon Is revealed that exon PII-containing transcripts were translated more effectively than exon I.3-containing transcripts. These findings explain why aromatase activity is higher in cells with the PII-containing transcripts than is cells with the I.3-containing transcripts. Our results indicate that aromatase is functionally expressed in human ovarian surface epithelial cells and its expression is regulated at both the transcriptional and translational levels.

This article has been cited by other articles:

				W.-P. Hu, S. K. Tay, and Y. Zhao Endometriosis-Specific Genes Identified by Real-Time Reverse Transcription-Polymerase Chain Reaction Expression Profiling of Endometriosis Versus Autologous Uterine Endometrium J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 228 - 238. [Abstract] [Full Text] [PDF]

				Y. Kinoshita and S. Chen Induction of Aromatase (CYP19) Expression in Breast Cancer Cells through a Nongenomic Action of Estrogen Receptor {alpha} Cancer Res., July 1, 2003; 63(13): 3546 - 3555. [Abstract] [Full Text] [PDF]

				S. CHEN, D. ZHOU, T. OKUBO, Y.-C. KAO, E. T. ENG, B. GRUBE, A. KWON, C. YANG, and B. YU Prevention and Treatment of Breast Cancer by Suppressing Aromatase Activity and Expression Ann. N.Y. Acad. Sci., June 1, 2002; 963(1): 229 - 238. [Abstract] [Full Text] [PDF]