Cooperation of Bcl-xL and c-Myc in Mammary Tumorigenesis
Annual rept. 1 Aug 1998-31 Jul 1999
GEORGETOWN UNIV WASHINGTON DC
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C-Myc is amplified in 16, rearranged in 5, and overexpressed in nearly 70 of all human breast cancers and it regulates both proliferation and apoptosis. BC1-xL, known to inhibit apoptosis potentially by modulating mitochondrial permeability and caspase activation, is overexpressed in some breast tumors and derivative cell lines. Pro-apoptotic Bax has been shown to be significantly reduced or altogether absent in many breast tumors and cell lines. Evidence from c-MycTGF-a bitransgenic mice suggests that escape from c-Myc-induced apoptosis may be necessary for continued cell cycle progression and neoplastic development. The focus of this study is the resolution of the role of Bcl-xL overexpression and Bax loss in cooperation with c-Myc overexpression in mammary tumorigenesis constitutive expression of Bcl-xL and loss of Bax likely disrupt the c-Myc-induce apoptotic pathways without significant alteration in c-Myc-mediated proliferation. c-Myc transgenicBax-knockout and c-MycBcl-xL bitransgenic mice have been generated, genotyped, and shall be assessed for altered tumor onset, incidence, growth, and pathological molecular characteristics once mammary tumors arise. Utilization of these models will aid in the dissection of the role of apoptosis in the development of breast cancer.
- Anatomy and Physiology
- Medicine and Medical Research