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Overexpression of the β Subunit of Human Chorionic Gonadotropin Promotes the Transformation of Human Ovarian Epithelial Cells and Ovarian Tumorigenesis.
MedLine Citation:
PMID:  21763678     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Ovarian carcinoma is the most lethal gynecologic malignancy, but underlying molecular events remain elusive. Expression of human chorionic gonadotropin β subunit (β-hCG) is clinically significant for both trophoblastic and nontrophoblastic cancers; however, whether β-hCG facilitates ovarian epithelial cell tumorigenic potential has been uncharacterized. Immortalized nontumorigenic ovarian epithelial T29 and T80 cells stably overexpressing β-hCG were examined for alterations in cell cycle and apoptotic status by flow cytometry, expression of proteins regulating cell cycle and apoptosis by Western blot, proliferation status by MTT assay, anchorage-independent colony formation, and mouse tumor formation. β-hCG IHC reactivity was evaluated on mouse xenografts and on human normal ovarian, fallopian tube, endometrium, and ovarian carcinoma tissues. T29 and T80 cells overexpressing β-hCG demonstrated significantly increased proliferation, anchorage-independent colony formation, prosurvival Bcl-X(L) protein expression, G2-phase progression, elevated cyclins E/D1 and Cdk 2/4/6, and decreased apoptosis. Collectively, these transformational parameters facilitated increased xenograft tumorigenesis (P < 0.05). β-hCG was elevated in malignant ovarian tumors, compared with normal epithelial expression in ovaries, fallopian tube, and endometrium (P < 0.001). Our data indicate that elevated β-hCG transforms ovarian surface epithelial cells, facilitating proliferation, cell cycle progression, and attenuated apoptosis to promote tumorigenesis. Our results further decipher the functional role and molecular mechanism of β-hCG in ovarian carcinoma. β-hCG may contribute to ovarian cancer etiology, which introduces a new therapeutic intervention target for ovarian cancer.
Authors:
Xiaoqing Guo; Guangzhi Liu; Isaiah G Schauer; Gong Yang; Imelda Mercado-Uribe; Fan Yang; Shiwu Zhang; Yuanli He; Jinsong Liu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-14
Journal Detail:
Title:  The American journal of pathology     Volume:  -     ISSN:  1525-2191     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; Department of Obstetrics and Gynecology, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
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