Regulators of apoptosis in human breast cancer

Objectives: Apoptosis or programmed cell death represents a mechanism by wh ich tumor cells with DNA damage can be deleted, Bcl-2 and p53 gene products have been both linked to apoptosis. Bcl-2 plays a role as an inhibitor of apoptosis that may extend the viability of cells containing genetic alterat ions and facilitate tumor progression. Mutant p53 has a similar effect. The purpose of this study was to investigate expression of bcl-2 in 70 maligna nt and 30 benign breast lesions using different methods (enzyme immunoassay , immunodot blot, Western blot) and to compare it with the established clin icopathological prognostic factors (age, tumor size, type, grade. lymph nod e status) and some molecular genetic markers in breast cancer. Results: bcl-2 and mutant p53 were highly expressed in breast cancer than b enign breast lesions and aneuploidy was more frequently detected in maligna nt breast samples, No correlation could be observed between bcl-2 expressio n acid node status, tumor size, differentiation, type, age at excision or m utant p53 expression. However, a strong positive associations were seen bet ween bcl-2 and estrogen receptors (ER), DNA aneuploidy. Eighty-five percent of bcl-2 positive tumors were ER positive and 65% were aneuploid, white in bcl-2 negative tumors only 28% were ER positive and 37% were aneuploid. Conclusions: The association seen between bcl-2 and ER raises the possibili ty that bcl-2 is an ER-regulated gene which suggests a potential important role for bcl-2 as a modulator of response to hormonal therapy in breast can cer. Monitoring hormonal therapy can easily be done by bcl-2 quantitative E IA method. copyright (C) 1999 The Canadian Society of Clinical Chemists.