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Consequences Of The Loss Of P53, Rb1, And Pten: Relationship To Gefitinib Resistance In Endometrial Cancer, L. Albitar, M. Carter, S. Davies, Kimberly Leslie Feb 2013

Consequences Of The Loss Of P53, Rb1, And Pten: Relationship To Gefitinib Resistance In Endometrial Cancer, L. Albitar, M. Carter, S. Davies, Kimberly Leslie

Kimberly K. Leslie

OBJECTIVE: These studies demonstrate how loss of function mutations or downregulation of key tumor suppressors missing from type I and type II endometrial cancer cells contributes to carcinogenesis and to resistance to the EGFR inhibitor gefitinib (ZD1839). METHODS: Cell models devoid of tumor suppressors PTEN and RB1 or PTEN were studied. PTEN, RB1 and p53 expression was reinstated, and the effects on cell cycle, apoptosis, and cell cycle regulators were evaluated. RESULTS: In Ishikawa H cells that model type I endometrial cancer in the loss of PTEN and RB1, re-expressing PTEN and RB1 increased the apoptotic and G1 phases and …