We analyzed the predictive relevance of Bcl-2 expression on 6-year relapse-free and overall survival in lymph node-negative breast cancers in relation to pathologic (tumor size) and biologic ([3H]thymidine-labeling index, p53 protein expression, and estrogen receptor [ER] status) features.
Thus, loss of bcl-2 expression in breast cancer is associated with a range of molecular markers of poor prognosis and may define part of an ER-negative, EGFR-positive phenotype.
The observations from this study clearly indicate that Bcl-2 in human breast cancer is associated with ER status, and that expression is enhanced in ER+ve tumours following tamoxifen, in association with reduced cell proliferation.
We therefore propose that dysregulation of apoptosis contributes to the pathogenesis of breast cancer, at least in part, due to an imbalance between anti-apoptosis genes (such as bcl-2/bcl-x) and apoptosis-promoting genes (bax).
We have analyzed bcl-2 protein expression by immuno-cytochemistry in primary node-positive breast cancers in two groups of patients (for a total of 180 cases).
Neither the presence nor the absence of bcl-2 expression significantly predicted disease-free survival or overall survival in patients with breast cancer.
Bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53 and an inverse correlation between Bcl-2 expression and p53 mutation has been observed in breast cancer and glioma.
Therefore, we propose that dysregulation of apoptosis might contribute to the pathogenesis of breast cancer at least in part due to an imbalance between members of the bcl-2 gene family.
Recently we have shown that the expression of bax-alpha, a death-promoting member of the bcl-2 family, is down-regulated in breast cancer and have provided evidence that low bax expression might contribute to the pathogenesis of breast cancer.
From these results, we infer the existence of hormonal regulation of Bcl-2 expression and evoke a novel role for estradiol and progestin in the genesis of breast cancer.
We analyzed the predictive role of p53 and bcl-2 expression, alone and in association with other variables, in postmenopausal women with node-positive, estrogen receptor-positive (ER+) breast cancers treated with radical or conservative surgery plus radiotherapy and adjuvant tamoxifen for at least 1 year.
To determine whether apoptosis loss at diagnosis is associated with the metastatic advantage of ductal breast carcinomas and to examine the relationship between Bcl-2 expression, p53, and tumor cell death status, we examined tumor samples from 116 patients diagnosed with T1 (2 cm or less) breast cancer with (n = 49) or without (n = 67) lymph node metastases.
It was concluded that estrogen and mutant p53 are related to the regulation of Bcl-2 expression and that the ability to prevent tumor cell death due to Bcl-2 can be developed by breast cancers.
Bax, one of the bcl-2 family genes, is expressed in a number of untransformed cell lines and various breast tissues, whereas only weak or no expression has been detected in breast cancer cell lines and malignant breast tissue.
The utility of biomarkers involved in DNA damage repair (p53 protein), control of programmed cell death (p53 and Bcl-2 proteins), and cellular detoxification (glutathione S-transferase-pi [GST-pi] enzyme) in predicting local breast cancer recurrence was analyzed retrospectively in two cohorts of breast cancer patients.
The purpose of this study was to evaluate bcl-2 and p53 expression in normal breast epithelia cells, as well as in intraductal and invasive cancerous lesions of breast cancer tissue using an immunohistochemical method and to clarify their role in the development of breast cancer.
Modulation of Bcl-2 protein levels by an intracellular anti-Bcl-2 single-chain antibody increases drug-induced cytotoxicity in the breast cancer cell line MCF-7.
Loss of Bcl-2 expression was strongly correlated with increased apoptotic and necrotic cell death, high proliferation rate and high tumour grade, supporting a model in which Bcl-2 not only mediates cell death, but also cell division in breast cancer tissue, and in which regulation of cell division and cell death are tightly linked.