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Identification of differentially expressed genes in MNU-induced rat mammary adenocarcinomas and their modulation by several chemopreventive agents

Posted on:2002-03-01Degree:Ph.DType:Dissertation
University:Medical College of Ohio at ToledoCandidate:Hu, LanFull Text:PDF
GTID:1464390011492463Subject:Biology
Abstract/Summary:
In the United States, approximately one in nine women will develop breast cancer in their life time. More than 180,000 women in the U.S. have been diagnosed with this disease each year. Despite the advancement in early diagnosis and treatment, the mortality rate of breast cancer virtually remains the same in the passed few decades. More understanding about the mechanisms of breast cancer development and progression is needed for improving breast cancer control. In light of such a situation, we designed a profiling study to identify differentially expressed genes in rat mammary adenocarcinomas in hope that the expression profile will improve the understanding of the mechanisms and provide new targets for diagnosis, treatment and prevention of breast cancer. Competitive cDNA Library Screening and cDNA array analysis were both used as the principle methodologies in our study. In the end, 202 clones including 100 known genes and 105 unknown clones were identified to differentially express in MNU-induced rat mammary adenocarcinomas. Many of these clones with known functions are for the first time reported to correlate with mammary carcinogenesis.; Cancer chemoprevention has been proven to be a promising means of controlling cancer development with administration of synthesized or naturally occurring substances. Among the chemopreventive agents studied, DHEA, Vorozole and Tamoxifen have demonstrated significant chemopreventive efficacy on mammary tumor development in animal models and/or clinical trials conducted in the high-risk population. In our study, we addressed the modulation effects of these three potential chemopreventive agents on the differentially expressed genes found in rat mammary adenocarcinomas. 30, 19 and 22 clones were found to be modulated by DHEA, Vorozole and Tamoxifen in our study respectively. These identified genes that are modulated by these chemopreventive agents may become potential intermediate endpoints in the future clinical trials.
Keywords/Search Tags:Rat mammary adenocarcinomas, Chemopreventive agents, Differentially expressed genes, Breast cancer
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