B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells.
B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells.
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B细胞淋巴瘤6蛋白刺激人乳腺癌细胞的致癌性
DOI：
10.1186/1471-2407-14-418
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发表时间：
2014-06-10
期刊：
影响因子：
3.8
通讯作者：
Wu ZS
中科院分区：
文献类型：
--
作者：
Wu Q;Liu X;Yan H;He YH;Ye S;Cheng XW;Zhu GL;Wu WY;Wang XN;Kong XJ;Xu XC;Lobie PE;Zhu T;Wu ZS
B细胞淋巴瘤6（BCL6）蛋白是一种进化上保守的锌指转录因子，除了在淋巴系统的恶性肿瘤中高表达外，在多种人类癌症中也显示高表达。本研究探讨了BCL6表达在乳腺癌中的作用及其在乳腺癌患者中的临床意义。
采用原位杂交和免疫组织化学方法对127例乳腺癌患者、50例乳腺良性疾病患者以及乳腺细胞系中BCL6蛋白的表达进行评估。分别使用BCL6 cDNA和siRNA在两种乳腺癌细胞系（MCF - 7和T47D）中恢复或敲低BCL6的表达。利用细胞活力MTT法、Transwell侵袭实验、集落形成实验和流式细胞术以及异种移植小鼠模型评估这些乳腺癌细胞系的表型变化。采用荧光素酶报告基因、免疫印迹和定量实时聚合酶链反应（qRT - PCR）研究乳腺癌细胞中BCL6表达调控后的分子事件。
BCL6蛋白在乳腺癌细胞系和组织标本中高表达，且BCL6蛋白的表达与乳腺癌患者的疾病进展和不良生存相关。在体外，BCL6的强制表达导致乳腺癌细胞系的增殖增加、非贴壁生长、迁移、侵袭和存活能力增强，而敲低BCL6表达则降低了乳腺癌细胞的这些致癌特性。此外，在裸鼠异种移植模型中，BCL6的强制表达增加了肿瘤的生长和侵袭性。在基因水平上，BCL6是miR - 339 - 5p的靶基因。BCL6的表达诱导CXCR4和细胞周期蛋白D1蛋白的表达。
本研究证明了BCL6在乳腺癌中的致癌特性，进一步的研究可将BCL6作为乳腺癌一种新的潜在治疗策略的靶点。
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 usingin situhybridization 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.
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DOI：
10.1186/bcr3054
发表时间：
2011
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Banerjee A;Wu ZS;Qian P;Kang J;Pandey V;Liu DX;Zhu T;Lobie PE
通讯作者：
Lobie PE
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影响因子：
3.8
作者：
Wu ZS;Wang CQ;Xiang R;Liu X;Ye S;Yang XQ;Zhang GH;Xu XC;Zhu T;Wu Q
通讯作者：
Wu Q
影响因子：
10.5
作者：
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通讯作者：
Bernards, R
DOI：
10.1006/bbrc.1998.8551
发表时间：
1998-06-18
影响因子：
3.1
作者：
Bajalica-Lagercrantz, S;Piehl, F;Lagercrantz, J
通讯作者：
Lagercrantz, J
DOI：
10.1186/bcr3441
发表时间：
2013-06-20
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dai M;Al-Odaini AA;Fils-Aimé N;Villatoro MA;Guo J;Arakelian A;Rabbani SA;Ali S;Lebrun JJ
通讯作者：
Lebrun JJ