Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium.
Alterations in p53 and Rb pathways are observed frequently in epithelial ovarian cancer (EOC).However, their roles in EOC initiation remain uncertain. Using a single intrabursal administration of recombinant adenovirus expressing Cre, we demonstrate that concurrent inactivation of p53 and Rb1 is sufficient for reproducible induction of ovarian epithelial carcinogenesis in mice homozygous for conditional gene alleles. Similarly to progression of disease in women, ovarian neoplasms spread i.p., forming ascites, and metastasize to the contralateral ovary, the lung, and the liver. These results establish critical interactions between p53 and Rb1 pathways in EOC pathogenesis, and provide a genetically defined immunocompetent mouse model of sporadic EOC.
Flesken-Nikitin
Andrea
A
Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853-6401, USA.
Choi
Kyung-Chul
KC
Eng
Jessica P
JP
Shmidt
Elena N
EN
Nikitin
Alexander Yu
AY
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D017931:DNA Primers; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology; D005260:Female; D017930:Genes, Reporter; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D051379:Mice; D008822:Mice, Transgenic; D010051:Ovarian Neoplasms / Q000235:genetics*; D010053:Ovary / Q000473:pathology*; D016133:Polymerase Chain Reaction; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*
D017931:DNA Primers; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53