Role of Bcl-2 in Breast Cancer Progression
Annual rept. 1 Aug 1998-31 Jul 1999
WAYNE STATE UNIV DETROIT MI
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Cyclin D1 expression is co-regulated by growth factor signaling and by cell adhesion signaling. Integrins mediate cell adhesion to the extracellular matrix and transduce biochemical signals, including activation of focal adhesion kinase. Upon the loss of cell adhesion, cyclin D1 expression is downregulated, and followed by apoptosis in normal epithelial cells. Since bcl-2 prevents apoptosis induced by the loss of cell adhesion, we hypothesized that bcl-2 induces survival signaling complementary to cell adhesion-mediated gene regulation. We showed that bcl-2 overexpression induces cyclin D1 expression in MCFlOA cells. Transient transfection studies confirmed bcl-2 induction of cyclin D1 promoter activity in MCFlOA, BT549, and MCF-7 cells in an anchorage-independent manner. We provide evidence that bcl-2 induction of cyclin D1 involves constitutive activation of focal adhesion kinase. The present study suggests a novel bcl-2 oncogenic activity through cyclin D1 induction, and also provides an insight into the distinct proliferation-independent pathway leading to increased cyclin D1 expression in breast cancer.
- Anatomy and Physiology
- Medicine and Medical Research