Cancer Research AACR Conference on Molecular Diagnostics - 2008 AACR Conference on Molecular Diagnostics - 2008
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[Cancer Research 60, 867-872, February 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

The Glucocorticoid Receptor Mediates a Survival Signal in Human Mammary Epithelial Cells1

Timothy J. Moran, Stacy Gray, Christina A. Mikosz and Suzanne D. Conzen2

Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois 60637

Complex autocrine and paracrine signaling pathways control the multiple cycles of epithelial cell proliferation and involution characteristic of the human mammary gland. Activation of these pathways can lead to cell division, cell cycle arrest, apoptosis, or survival; their aberrant regulation often contributes to malignant transformation. In this report, we show that glucocorticoid signals a potent survival pathway in the immortalized human mammary epithelial cell line MCF10A. Withdrawal of glucocorticoid from defined media triggers apoptosis, despite the presence of epidermal growth factor and insulin. Apoptosis is accelerated by ectopic expression of c-Myc and blocked by overexpression of Bcl2. Although MCF10A cells can undergo apoptosis after CD95/Fas receptor activation, cell death caused by glucocorticoid withdrawal is independent of CD95/Fas receptor signaling. The mechanism through which glucocorticoid inhibits apoptosis is also independent of phosphatidylinositol 3-kinase activity and its downstream target Akt, thus establishing the existence of a novel epithelial cell survival pathway mediated by glucocorticoids.




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