Conditional knockout of brca1/2 and p53 in mouse ovarian surface epithelium: do they play a role in ovarian carcinogenesis?
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.
Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Ki-Yon
KY
Kim
Dong Wook
DW
Park
Eui-Bae
EB
Jeung
Kyung-Chul
KC
Choi
D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004848:Epithelium / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D051379:Mice; D018345:Mice, Knockout; D010051:Ovarian Neoplasms / Q000235:genetics*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D019313:BRCA1 Protein; D024682:BRCA2 Protein; C106711:BRCA2 protein, mouse; D016326:Extracellular Matrix Proteins; D016159:Tumor Suppressor Protein p53; C077112:Lox protein, mouse; D008249:Protein-Lysine 6-Oxidase