Gene expression analysis of ovarian tumors from mice with knockout of DICER and PTEN

The cell of origin of serious ovarian cancer is unknown. To create a mouse model for this lethal cancer and identify early cancer biomarkers, we conditionally deleted both Dicer (essential for microRNA biosynthesis) and Pten (a negative regulator of the PI3K pathway) in the female reproductive tract. Beginning at ~3-5 months, these Dicer/Pten mutant mice develop high-grade serious carcinomas that initiate in the stroma of the fallopian tube through a mesenchymal-to-epithelial transition (MET), subsequently envelop the ovary, and then metastasize throughout the peritoneum, resulting in ascites and 100% lethality by 13 months. The fallopian tube cancers demonstrate upregulation of genes encoding known and novel secreted proteins that are potential biomarkers. This study uncovers a new paradigm for the initiation of high-grade serous ovarian cancer.

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Kim J, Coffey DM, Creighton CJ, Yu Z, Hawkins SM, Matzuk MM