Exploiting bcl-2 Overexpression in the Chemotherapy of Breast Cancer
Annual rept. 1 Jun 1998-31 May 1999
CHILDREN'S HOSPITAL OF PITTSBURGH PA
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In neural crest cells, bcl-2 overexpression results in altered handling of glutathione, and consequent increased cellular reducing potential. This change potentiates the induction of apoptosis by enediyne prodrugs in neural crest tumor cells. Our studies examined the applicability of these findings to MCF-7 breast cancer cells, known to overexpress bcl-2 in response to estradiol treatment. We have found that estradiol treatment of MCF-7 cells does indeed result in an increase in the expression of bcl-2. However, transfection of MCF-7 cells with an expression construct for bcl-2 does not result in potentiation of enediyne-induced apoptosis. Unlike the case for neural crest tumor cells, glutathione handling is not altered in MCF-7 cells induced by transfection to overexpress bcl-2. Our results to date suggest that determination of the effect of bcl-2 expression on glutathione handling may allow prediction of the response of a particular tumor cell to treatment with enediynes. In the one-year extension period of this grant, we will merge these two lines of investigation and determine the effects of estradiol treatment rather than direct bcl-2 transfection on glutathione handling in MCF-7 cells. Initial studies indicate that estradiol treatment does alter the native glutathione content of MCF-7 cells.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research