Clinical significance of bcl-2 gene expression in human breast cancer tissues

Abstract

The expression of estrogen receptor (ER) and bcl-2 (Bcl-2), an apoptosis protective oncogene, in normal and cancerous breast duct epithelia was immunohistochemically examined in fresh frozen tumor tissues from 142 Japanese breast cancer patients. The clinico-pathological characteristics and the disease free survival of the patients were analyzed. The expression of both the proteins was also observed in intraductal components of breast cancer. Although less than 1% of normal duct epithelia expressed ER, Bcl-2 was diffusely expressed. The expression of both these proteins in breast cancer significantly correlated with each other. Their expression significantly correlated negatively with tumor size but not with lymph node status. The papillo-tubular sub-type of invasive ductal carcinoma expressed Bcl-2 significantly more frequently than the solid-tubular sub-type. Patients with Bcl-2 expressing tumors survived without recurrence significantly more than those with tumors exhibiting reduced expression. Papillary-cribriform type intraductal components expressed both those proteins more often than the solid-comedo type.

Differential anti-tumor activity of coriolus versicolor (Yunzhi) extract through p53- and/or Bcl-2-dependent apoptotic pathway in human breast cancer cells

“…Noninvasive or early-stage (mostly ER-positive) breast cancer cells usually have high Bcl-2 expression, while invasive or metastatic (mostly ER-negative) breast cancers often have lower expression of Bcl-2 protein. 45,46 In the present study, the lack of Bcl-2 suppression implicated that the apoptosis of MDA-MB-231 cells induced by the CV extract was probably mediated via a Bcl-2-independent pathway (Fig. 3B).…”

Apoptosis Inhibitor as a Suppressor of Tumor Progression: Expression of Bcl-2 Eliminates Selective Advantages for p53-Deficient Cells in the Tumor

“…Being a potential oncogene, at least in hematopoetic tumors (where its expression is correlated with poor prognosis) Bcl-2-overexpression positively correlates with favorable clinical outcome in breast, ovarian and some other solid cancers. [5][6][7][8][9][10][11][12][13][14][22][23] It is noteworthy that even in the hematopoetic tumors Bcl-2 expression had no influence on overall survival but was rather associated with rapid tumor growth and reduced therapeutic response. 24 The existing explanation of Bcl-2 associated favorable prognosis based on the observation of a decreased proliferation of Bcl-2-overexpressing cells 7 was not confirmed by our data, although there was no difference in growth rates of the cells in vitro.…”

“…However, there are reports indicating that these two genetic alterations have opposite prognostic values in some types of cancer: while the inactivation of p53 is associated with rapid progression and considered a negative prognostic factor, [5][6][7]9 the expression of Bcl-2 was often found to be associated with favorable prognosis in breast, ovarian and some other solid cancers. [5][6][7][8][9][10][11][12][13][14] Thus, Bcl-2 expression in breast cancer positively correlates with estrogen receptor expression, normal ploidy, higher histological tumor grade and absence of metastases, 5,6,14 suggesting that Bcl-2 in tumors somehow delays tumor progression.…”

Anti-oestrogen resistant human breast cancer cell lines are more sensitive towards treatment with the vitamin D analogue EB1089 than parent MCF-7 cells

“…Furthermore, they all lack PR expression (Lykkesfeldt et al, 1994(Lykkesfeldt et al, , 1995. Several clinical studies have shown that the Bcl-2 expression in breast tumours is strongly correlated to both ERα and PR expression, and Bcl-2 expression is an indicator of a favourable outcome following endocrine treatment (Gee et al, 1994;Lipponen et al, 1995;Silvestrini et al, 1996;Elledge et al, 1997;Keen et al, 1997;Kobayashi et al, 1997;Olopade et al, 1997;Holmqvist et al, 1999). The decreased Bcl-2 expression associated with decreased ERα expression, and lack of response to antioestrogens observed in the resistant cell lines is in concert with the above-mentioned clinical studies.…”