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KMID : 0893420100110040291
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Journal of Veterinary Science
2010 Volume.11 No. 4 p.291 ~ p.297
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Conditional knockout of brca1/2 and p53 in mouse ovarian surface epithelium: Do they play a role in ovarian carcinogenesis?
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Kim Ki-Yon
Park Dong-Wook
Jeung Eui-Bae
Choi Kyung-Chul
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Abstract
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Alterations of genes are known to be critical for the induction of tumorigenesis, but the mechanism of ovarian carcinogenesis is little understood and remains to be elucidated. In this study, we investigated the roles of brca1, brca2 and p53 genes in the development of ovarian cancer using conditional knockout mice generated by a Cre-loxP recombinant system. Following the application of recombinant adenovirus expressing Cre in vitro, the proliferation of ovarian surface epithelium (OSE) was increased. For instance, a significant increase in cell growth was observed in OSE cells in vitro by conditional knockout isolated from the mice bearing concurrent floxed copies of brca1 and brca2/p53. However, the proliferative effect of the ovarian cells was not observed in concurrent brca1/brca2 or p53 knockout mice in vivo, indicating that we could not observe the direct evidence of the involvement of brca1, brca2, and p53 in ovarian carcinogenesis. Since morphological changes including tumor formation were not observed in mice bearing floxed copies of concurrent brca1/brca2 or p53, the inactivation of brca1/2 or p53 is not sufficient for the induction of tumor formation. Taken together, these results suggest that the deficiency of these genes may not be involved directly in the mechanism of ovarian carcinogenesis.
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KEYWORD
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brca, p53, conditional knockout, ovarian cancer, tumor suppressor genes
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