Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer.
Epithelial ovarian tumors present a complex clinical, diagnostic and therapeutic challenge because of the difficulty of early detection, lack of known precursor lesions and high mortality rates. Endometrioid ovarian carcinomas are frequently associated with endometriosis, but the mechanism for this association remains unknown. Here we present the first genetic models of peritoneal endometriosis and endometrioid ovarian adenocarcinoma in mice, both based on the activation of an oncogenic K-ras allele. In addition, we find that expression of oncogenic K-ras or conditional Pten deletion within the ovarian surface epithelium gives rise to preneoplastic ovarian lesions with an endometrioid glandular morphology. Furthermore, the combination of the two mutations in the ovary leads to the induction of invasive and widely metastatic endometrioid ovarian adenocarcinomas with complete penetrance and a disease latency of only 7 weeks. The ovarian cancer model described in this study recapitulates the specific tumor histomorphology and metastatic potential of the human disease.
Dinulescu
Daniela M
DM
Center for Cancer Research, Massachusetts Institute of Technology, 40 Ames Street, Cambridge, Massachusetts 02139, USA.
Ince
Tan A
TA
Quade
Bradley J
BJ
Shafer
Sarah A
SA
Crowley
Denise
D
Jacks
Tyler
T
D000818:Animals; D004195:Disease Models, Animal; D004715:Endometriosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051379:Mice; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D025521:Tumor Suppressor Proteins; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D018631:ras Proteins