Disease Heterogeneity and Immune Biomarkers in Preclinical Mouse Models of Ovarian Carcinogenesis
Abstract
Ovarian epithelial tumors are highly diverse and the exact tissue of origin is still unclear. Although the ovarian surface epithelial cells (OSEs) are believed to be the originating site, more recent evidence suggests that the ovarian tumors could instead arise directly from extraovarian tissues that are embryologically derived from the m llerian ducts. Using genetically engineered mice (Cre-loxP) with conditional mutations in the Kras and PI3K/Pten pathways (KrasPten mice), we demonstrated in year one that activation of these oncogenic pathways in the peritoneal cavity, may lead to ovarian tumors that are histomorphologically identical to those arising in mice with Kras and PI3K pathways activated in the OSE only. Further validation of these novel findings via expression profiling is currently in progress. If confirmed, our work may lead to identification of a new paradigm in ovarian tumorigenesis, one that may not require the involvement of the OSE. We also identified for the first time that activation of the Kras and PI3K pathways in the uterine lining leads to endometrial hyperplasia, a premalignant condition, predisposing to endometrial adenocarcinoma. This animal model would provide unparalleled opportunities for studies on premalignant and malignant lesions of the female genital tract, with secondary ovarian involvement.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2011
- Accession Number
- ADA598467
Entities
People
- Anda Vlad