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Gene expression profile of epithelial ovarian tumor tissue of a transgenic mouse model compared to normal mouse ovary tissue

ABSTRACT: The etiology of ovarian cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mouse model termed ERalpha d/d in which a conditional deletion of estrogen receptor alpha (ERalpha) gene occurred in the anterior pituitary, but ERalpha expression remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to elevated production of luteinizing hormone (LH) by this tissue. Hyperstimulation of ovarian cells by LH resulted in increased steroidogenesis, leading to high circulating levels of progesterone, testosterone and E. The ERalpha d/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age, and by 12 months, most mice carrying these tumors died. Besides proliferating epithelial cells, these tumors also contained an expanded population of stromal cells, which express P450 aromatase suggesting that these cells acquired the ability to synthesize E. In ERalpha d/d mice, in response to the E produced by the stromal cells, the ERalpha signaling is accentuated in the ovarian epithelial cells, triggering increased ERalpha-dependent gene expression, abnormal cell proliferation, and tumorigenesis. The ERalpha d/d animal model of ovarian epithelial tumorigenesis will serve as a powerful tool for exploring the involvement of E-dependent signaling pathways in the etiology of ovarian cancer. To identify aberrantly regulated genes in epithelial ovarian tumors, we performed gene expression profling of ovarian tumor tissue isolated from ERaplha d/d mice and normal ovary tissue isolated from ERaplha f/f control mice. The ERalpha d/d mouse model was created via conditional deletion of ERalpha by employing the Cre-LoxP strategy. Transgenic mice expressing Cre recombinase under the control of progesterone receptor (PR) promoter, termed PR-cre mice, were crossed with mice harboring the ‘floxed’ ERalpha gene (ERalpha f/f) to create the ERalpah d/d mice in which the ERalpha gene is deleted in cells expressing PR. Ovarian tumor tissue was isolated from ERalpha d/d mice and normal ovary tissue was isolated from ERalpha f/f mice at 5 months and 10 months of age. Tissues were snap frozen and total RNA was isolated. Total RNA was pooled from 3 mice for each sample subjected to microarray analysis.

ORGANISM(S): Mus musculus  

TISSUE(S): Ovary, Ovarian Tumor

SUBMITTER: Mary J Laws   Mary Laws  Indrani C Bagchi  Milan K Bagchi 

PROVIDER: E-GEOD-39402 | ArrayExpress | 2013-08-06



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