KRAS mutation coupled with p53 loss is sufficient to induce ovarian carcinosarcomas in mice

Feng‐Hsiang Tang, Tang FH, Feng-Hsiang Tang, Hsieh TH, Tsung‐Hua Hsieh, Tsung-Hua Hsieh, Chia-Yi Hsu, Chia‐Yi Hsu, Hsiao-Yun Lin, Hsiao‐Yun Lin, Lin HY, Cheng‐Yu Long, Cheng-Yu Long, Kuang‐Hung Cheng, Cheng KH, Kuang-Hung Cheng, Eing-Mei Tsai, Eing‐Mei Tsai, Tsai EM
International journal of cancer · 2016 · vol. 140(8) , pp. 1860–1869 · doi:10.1002/ijc.30591 · PMID:28032649 · W2564785818
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Concomitant KRAS mutation and p53 loss in mouse ovarian surface epithelium induces metastatic ovarian carcinosarcomas that recapitulate human disease histomorphology and malignant transformation mechanisms.

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Abstract

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.

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Condition tags

endometriosis

MeSH descriptors

Carcinosarcoma Ovarian Neoplasms Proto-Oncogene Proteins p21(ras) Tumor Suppressor Protein p53 Animals Carcinosarcoma Carcinosarcoma Cell Line, Tumor Cell Proliferation Cell Proliferation Cell Transformation, Neoplastic Cell Transformation, Neoplastic Disease Models, Animal Female Humans Mice Mice, Transgenic Mutation Ovarian Neoplasms Ovarian Neoplasms

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