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. Here we evaluated for the first time the expression of cell death-related proteins Bcl-2 and Bax in hyperplastic, premalignant (carcinoma in situ), or malignant (carcinoma) lesions of mammary carcinogenesis; we also assessed whether these proteins are involved in mediating Vz-induced cell death in tumors. We found that Bcl-2 and Bax 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 expression. Bcl-2 and Bax levels in hyperplastic lesions were similar to those of normal mammary epithelial cells but lower in most carcinomas in situ and carcinomas. In animals with established mammary tumors, Vz induced apoptotic cell death, which was primarily associated with a decrease in Bcl-2 and, to a lesser extent, with a decrease in Bax. These data support the hypothesis that Bcl-2 loss is more potent than Bax gain in regulating apoptotic cell death in mammary tumors.
Shilkaitis
A
A
Department of Surgical Oncology, University of Illinois at Chicago, 60612, USA.
Graves
J
J
Mehta
R R
RR
Hu
L
L
You
M
M
Lubet
R
R
Steele
V
V
Kelloff
G
G
Christov
K
K
D000818:Animals; D017209:Apoptosis; D047072:Aromatase Inhibitors; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006965:Hyperplasia / Q000378:metabolism* / Q000473:pathology; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
D047072:Aromatase Inhibitors; C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014230:Triazoles; D051028:bcl-2-Associated X Protein; C060523:vorozole