Bcl-2 and Bax are differentially expressed in hyperplastic, premalignant, and malignant lesions of mammary carcinogenesis

Previously, we found that vorozole (Vz), a nonsteroidal aromatase inhibitor , suppresses the development and progression of mammary tumors in rats. Her e we evaluated for the first time the expression of cell death-related prot eins Bcl-2 and Bar in hyperplastic, premalignant (carcinoma in situ), or ma lignant (carcinoma) lesions of mammary carcinogenesis; we also assessed whe ther these proteins are involved in mediating Vz-induced cell death in tumo rs. We found that Bcl-2 and Bar were equally expressed in epithelial cells of terminal end buds, ducts, and alveoli. However, in myoepithelial cells, the level of Bax expression was much higher than the level of Bcl-2 express ion. Bcl-2 and Bar levels in hyperplastic lesions were similar to those of normal mammary epithelial cells but lower in most carcinomas in situ and ca rcinomas. In animals with established mammary tumors, Vt induced apoptotic cell death, which was primarily associated with a decrease in Bcl-2 and, to a lesser extent, with a decrease in Bar. These data support the hypothesis that Bcl-2 loss is more potent than Bar gain in regulating apoptotic cell death in mammary tumors.