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KRAS mutation coupled with p53 loss is sufficient to induce ovarian carcinosarcomas in mice
Author(s) -
Tang FengHsiang,
Hsieh TsungHua,
Hsu ChiaYi,
Lin HsiaoYun,
Long ChengYu,
Cheng KuangHung,
Tsai EingMei
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30591
Subject(s) - kras , ovarian cancer , malignant transformation , cancer research , ovary , clear cell , carcinosarcoma , endometriosis , biology , cancer , pathology , malignancy , medicine , carcinoma , colorectal cancer , endocrinology
Ovarian carcinosarcoma cancer is the most lethal form of gynecological malignancy, but the pathogenesis and biological function for this ovarian cancer remain unknown. We establishment the transgenic mouse model of K‐ras G12D p53 loxP/loxP and found that K‐ras mutation and p53 deletion within the ovarian surface epithelium gave rise to ovarian lesions with a hyperproliferation and endometrioid glandular morphology. Furthermore, double mutant ovaries formed ovarian carcinosarcomas that were high grade and poorly differentiated. Induction was widely metastatic and spread to abdominal organs including liver, spleen, and kidney at 4 wk. We also confirmed the role of K‐ras G12D in ovarian cancer cell lines MCAS and PA‐1 and showed that K‐ras G12D overexpression strongly induced cell proliferation, migration, and invasion. The ovarian cancer model we developed recapitulates the specific tumor histomorphology and the probable mechanism of malignant transformation in endometriosis.