Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 309, Issue 2, Pages 377-383Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2003.08.012
Keywords
Src; FAK; Akt; apoptosis; ovary; cancer
Categories
Funding
- NCI NIH HHS [CA 50616] Funding Source: Medline
- NICHD NIH HHS [HD 36013] Funding Source: Medline
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The vast majority of ovarian cancers originate in the ovarian surface epithelium. Unfortunately, there is a lack of appropriate animal models for ovarian cancer research. Spontaneously transformed mouse ovarian surface epithelial cells may provide a faithful animal model for human ovarian cancer. One such cell line (ID8) has been partially characterized. ID8 cells demonstrate constitutive Src tyrosine kinase activation with resulting phosphatidylinositol-3-kinase activation and Akt and forkhead phosphorylation. In addition. focal adhesion kinase is constitutively phosphorylated at tyrosine 925, a Src phosphorylation site, resulting in increased Ras activation. These features are common to human ovarian cancer cell lines. Inhibition of Src enhances the cell killing effects of both paclitaxel and cisplatinum. Finally, Src inhibition restores sensitivity of a drug resistant ID8 cell line. The ID8 mouse ovarian cancer cell line presents new opportunities to study ovarian cancer progression and pre-therapeutic trials in an immune competent background. (C) 2003 Elsevier Inc. All rights reserved.
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