Modeling Ovarian Cancer

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Science  16 Mar 2012:
Vol. 335, Issue 6074, pp. 1280-1281
DOI: 10.1126/science.335.6074.1280-d

Among the four types of epithelial ovarian cancer, which affects about 1.4 % of women, the serous type is found in 70% of ovarian cancer deaths. Studies have reported different origins for ovarian cancer—the ovary or fallopian tube. Kim et al. generated a double knockout mouse, eliminating the genes for Dicer, the enzyme that converts pre-microRNAs to mature microRNAs, and Pten, a tumor suppressor, in the reproductive tract, and found that serous carcinomas developed from the fallopian tube and then metastasized elsewhere. All of these mutant mice died within about 6 to 12 months. Single mouse knockouts did not show tumor development in the reproductive system. Abnormal cell proliferation started in the stromal compartment of the fallopian tube rather than the epithelial layer, and the cells underwent a stromal-to-epithelial transition. The cancers in the double mutant mice were similar phenotypically, histologically, and at the molecular level to those seen in humans. This work supports the idea of a fallopian tube origin of human high-grade serous ovarian carcinoma and provides a model system for future analyses of this deadly cancer in women.

Proc. Natl. Acad. Sci. U.S.A. 109, 10.1073/pnas.1201029109 (2012).

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