Sex hormone-induced mammary carcinogenesis in the female Noble rats: Expression of Bcl-2 and Bax in hormonal mammary carcinogenesis

We have established a Noble rat model to explore the mechanisms of hormonal mammary carcinogenesis, in which the role of androgen in promoting mammary carcinogenesis was highlighted. We have also established that stromal-epit helial interactions may be responsible for the promotional effects of testo sterone in mammary carcinogenesis. Based on these understandings, in the pr esent study we examined the expression of Bcl-2 and Bax in pre-malignant ma mmary glands from rats treated with different protocols of sex hormones for 7 weeks as well as sex hormone induced mammary tumours. We observed that B cl-2 was strongly expressed in most of mammary tumour cells, whereas weak o r negative in adjacent normal or hyperplastic ductal structures. On the con trary, Bax immunoreactivity was weak in mammary tumour cells while strongly expressed in adjacent normal or hyperplastic ductal structures. More impor tantly, the results from comparative study of 'pre-malignant' glands furthe r showed that when animals were treated with 17 beta-oestradiol, the mammar y epithelial cells expressed high levels of Bcl-2. The results from rats tr eated with testosterone, either alone or in combination with oestrogen, giv e rise to high levels of Bax expression in 'pre-malignant' mammary glands. These observations indicate that in 'pre-malignant' mammary glands, treatme nt with testosterone, either alone or in combination with 17 beta-oestradio l, may induce high apoptotic activities. However, in fully developed mammar y tumours, the apoptotic activities apparently decrease in tumour cells. TU NEL assay provides further data to support this conclusion. Our study, thus , suggests that androgens may play a promoting role in mammary carcinogenes is by upregulation of Bax expression and induction of high apoptotic activi ties in 'pre-malignant' stage, which would provide a selective pressure fav ouring the expansion of the initiated cells.