Role of Bc1-2 in Breast Cancer Progression.
Annual rept. 1 Aug 96-31 Jul 97,
WAYNE STATE UNIV DETROIT MI
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The anti-apoptotic gene bcl-2 is frequently overexpressed in many human tumors including invasive breast cancer. In vitro studies clearly demonstrate that the bcl-2 gene product prevents apoptosis following a variety of stimuli including radiation, hyperthermia, growth factor withdrawal and chemotherapeutic drugs. However, high levels of the bcl-2 expression have shown a positive correlation in clinicopathological studies, such as tumor grade and better response to hormonal treatment and chemotherapy. It is now critical to investigate the in vivo function of bcl-2 in human cells to elucidate the contradiction between clinical studies and in vitro studies. We have investigated the roles of bcl-2 in breast cancer development using MCF10A in vitro model and MCF10AT in vivo model. Here, we report that bcl-2 deregulates a G1S checkpoint in MCF10A cells through upregulation of G1 cyclin activities, suggesting a role of bcl-2 as an oncogene. We then show that bcl-2 induces transformed phenotype in MCF10AT cells as determined by a soft agar assay. Bcl-2 expressing MCF10AT cells will be utilized for in vivo studies.
- Medicine and Medical Research
- Anatomy and Physiology