Ovarian Cancer Origins

See allHide authors and affiliations

Science  30 Mar 2012:
Vol. 335, Issue 6076, pp. 1546
DOI: 10.1126/science.335.6076.1546-c

One to 2% of women will be diagnosed with ovarian cancer in their lifetimes. As a result, there is great interest in better understanding the molecular and cellular events that drive the development of this cancer. In fact, whether the ovary or fallopian tube gives rise to serous ovarian cancer, the subtype that causes 70% of ovarian cancer deaths, is still unknown. To investigate this question, Kim et al. generated mice with reproductive tract–specific deletions in Dicer, the enzyme that converts pre-microRNAs to mature microRNAs, and Pten, a tumor suppressor. They found that serous ovarian carcinomas developed from the fallopian tube and then metastasized elsewhere, killing all double knockout mice by 6 to 12 months of age. Mice singly deficient in these proteins, however, did not show tumor development in the reproductive system. Histological analysis revealed that abnormal cell proliferation started in the stromal compartment of the fallopian tube rather than the epithelial layer, with the cells undergoing a stromal-to-epithelial transition. The phenotypic, histological, and molecular characteristics of the cancers that developed in the double knockout mice were similar to those seen in humans. These mice may therefore provide a useful model system for studying serous ovarian cancer.

Proc. Natl. Acad. Sci. U.S.A. 109, 3921 (2012).

Navigate This Article