B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells

Abstract

BackgroundB-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients.MethodsExpression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells.ResultsBCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins.ConclusionsThe current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer.

MicroRNA-187 induces diffuse large B-cell lymphoma cell apoptosis via targeting BCL6

“…The BCL6 protein, a zinc finger transcription factor that has been conserved throughout evolution, has demonstrated high expression levels in numerous types of human cancer, alongside lymphoid system malignancies (19). Further studies have observed potent BCL6 protein expression in various types of human cancer outside of the lymphoid system.…”

OTUB1-catalyzed deubiquitination of FOXM1 facilitates tumor progression and predicts a poor prognosis in ovarian cancer

“…Standard avidin-biotin immunohistochemical analysis of the sections was performed. The staining results were evaluated by at least three certified pathologists and the tumor cell staining was scored as follows: For FOXM1, 0 (no staining for nucleus despite of the staining result of cytoplasm or membrane), 1 (weak staining for nucleus [and cytoplasm] and area of positive staining <10%), 2 (moderate staining for nucleus [and cytoplasm] and area of positive staining among 10%–50%), and 3 (strong staining for nucleus [and cytoplasm] and area of positive staining >50%) [42, 43]; for OTUB1, 0 (no staining for cytoplasm or membrane), 1(weak positive for cytoplasm), 2(moderate positive for cytoplasm), and 3(strong positive for cytoplasm). The cases with score 0-1 were considered low and those with a score of 2-3 were considered high [42, 43].…”

BCL6 induces EMT by promoting the ZEB1-mediated transcription repression of E-cadherin in breast cancer cells

“…BCL6 plays a role in promoting the invasion of breast cancer cells and the expression level of BCL6 positively associates with poor survival of breast cancer patients [5]. However, how BCL6 participates in the regulation of the development and progression of breast cancer remains unclear.…”

“…However, we did not detect any binding of BCL6 to the E-cadherin promoter (data not shown). A number of studies demonstrate that a variety of transcriptional repressors including Snail, Twist, Slug, deltaEF1/ZEB1, SIP1/ZEB2 and CtBP2 can bind to the E-cadherin promoter and inhibit the gene transcription [5][6][7][8][9][10][11][12]. We therefore screened which transcription repressor mediated the BCL6-repressed E-cadherin expression with siRNA assay.…”

“…The expression of BCL6 positively associates with the tumor-promoting function of CCND1 and HIF1α in invasive breast cancer [4]. Moreover, the expression level of BCL6 positively associates with poor survival of breast cancer patients [5]. Therefore, BCL6 has been found to have a potential acting as a therapeutic target for breast cancer [6].…”