Kim Ki-Yon, Park Dong Wook, Jeung Eui-Bae, Choi Kyung-Chul
Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
J Vet Sci. 2010 Dec;11(4):291-7. doi: 10.4142/jvs.2010.11.4.291.
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.
已知基因改变对于肿瘤发生的诱导至关重要，但卵巢癌发生的机制却鲜为人知，仍有待阐明。在本研究中，我们使用由Cre-loxP重组系统产生的条件性敲除小鼠，研究了brca1、brca2和p53基因在卵巢癌发生发展中的作用。在体外应用表达Cre的重组腺病毒后，卵巢表面上皮（OSE）的增殖增加。例如，通过从同时携带brca1和brca2/p53的floxed拷贝的小鼠中分离出的条件性敲除，在体外观察到OSE细胞的细胞生长显著增加。然而，在体内同时敲除brca1/brca2或p53的小鼠中未观察到卵巢细胞的增殖效应，这表明我们无法观察到brca1、brca2和p53参与卵巢癌发生的直接证据。由于在同时携带brca1/brca2或p53的floxed拷贝的小鼠中未观察到包括肿瘤形成在内的形态学变化，因此brca1/2或p53的失活不足以诱导肿瘤形成。综上所述，这些结果表明这些基因的缺陷可能不直接参与卵巢癌发生的机制。
