Protein expression of B-cell lymphoma gene 6 (BCL-6) in invasive breast cancer is associated with cyclin D1 and hypoxia-inducible factor-1α (HIF-1α)

Abstract

B-cell lymphoma gene (BCL-6) upregulation contributes to immortalization of mouse embryo fibroblast and primary B cells via upregulation of cyclin D 1 . As cyclin D 1 overexpression is a common phenomenon in different cancers, BCL-6 protein overexpression may not be restricted to lymphomas. In this study, expression of BCL-6 was investigated by immunohistochemistry on paraffin-embedded specimens from 150 breast cancer patients and 10 specimens of normal breast tissue. The results showed BCL-6 overexpression (X10% of cells) in 24/150 (16%) breast cancer patients, whereas in normal breast low expression (o1%) of BCL-6 was observed. In linear regression analysis BCL-6 expression was associated with cyclin D 1 (r ¼ 0.197, P ¼ 0.016). Further, in v 2 analyses, BCL-6-positivity was associated with overexpression of p53 (P ¼ 0.016), and hypoxia-inducible factor-1a (Po0.001). Involvement of BCL-6 in breast carcinogenesis is further underscored by comparative genomic hybridization analysis that showed gains at the BCL-6 locus (3q27) in 14/86 (16%) breast cancer tissues. The cases with amplification in BCL-6 showed an increased (25%) incidence of BCL-6 protein overexpression. Thus, this study is the first to show that BCL-6 oncogene activation plays a role in cancers other than lymphomas.

A Critical Role of miR-144 in Diffuse Large B-cell Lymphoma Proliferation and Invasion

“…For example, Chamdin and colleagues reported that the expression of BCL6 in neuroblastoma is significantly associated with poor survival of the patients (25). In addition, BCL6 protein is expressed in the mammary epithelium in nonpregnant animals and animals in early pregnancy (26); in murine mammary epithelium, BCL6 overexpression prevents duct formation and apoptosis (27). However, BCL6 protein is highly expressed in breast cancer tissues, especially in high-grade ductal breast cancer (26,27).…”

“…In addition, BCL6 protein is expressed in the mammary epithelium in nonpregnant animals and animals in early pregnancy (26); in murine mammary epithelium, BCL6 overexpression prevents duct formation and apoptosis (27). However, BCL6 protein is highly expressed in breast cancer tissues, especially in high-grade ductal breast cancer (26,27). Overall, the role of BCL6 protein in human cancers other than those in the lymphoid system remains to be determined.…”

Hypoxia in breast cancer

“…The results showed overexpression of BCL-6 in 16% of tested cancer lesions while unchanged tissue was characterized by overexpression in less than 1% of cases. The analysis showed that the increase in BCL-6 activity was correlated with increased expression of cyclin D1, p53 protein and HIF-1α [32]. The study was the first to demonstrate that BCL-6 plays an important role also in cancers other than lymphomas.…”

Morphological and quantitative analysis of BCL6 expression in human colorectal carcinogenesis

“…Indeed, BCL6 is targeted by genetic aberrations and acts as an oncogene in GC-derived lymphomas (2); despite this, its precise role in the malignant transformation process remains to be fully elucidated. In non-hematolymphoid neoplasms, BCL6 expression has been demonstrated in subsets of high grade ductal human carcinomas of the breast, both at the gene and the protein level (12,13).…”

“…Logarajah et al (12) and Bos et al (13) reported that BCL6 has an important function in breast cancer. Walters et al (14) evaluated the BCL6 protein expression in a subset of mesenchymal tumors.…”