BRG1 is a prognostic marker and potential therapeutic target in human breast cancer.

BRG1 is a prognostic marker and potential therapeutic target in human breast cancer.
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BRG1 是人类乳腺癌的预后标志物和潜在的治疗靶点。

DOI:
10.1371/journal.pone.0059772
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zheng J
Zheng J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bai J;Mei P;Zhang C;Chen F;Li C;Pan Z;Liu H;Zheng J

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BRG1是SWI/SNF染色质重塑复合体的核心成分,已被认为与癌症的发生有关;然而,BRG1在乳腺癌中的生物学意义尚不清楚。我们探讨了BRG1在人类乳腺癌发病机制中的作用。应用组织芯片和免疫组织化学方法,检测437例乳腺癌标本中BRG1的表达,探讨BRG1在乳腺癌细胞增殖、迁移和侵袭中的作用。我们的卡普兰-迈耶生存曲线显示,BRG1高表达与总体(P = 0.000)和疾病特异性(P = 0.000)5年患者生存率呈负相关。此外,我们还发现,通过RNA干扰抑制BRG1基因可以显著抑制细胞的增殖并导致细胞周期的停止。这种细胞增殖的减少是由于细胞周期蛋白D1和E被抑制,而p27被上调,导致细胞周期停滞于G1期。此外,BRG1的缺失诱导了TIMP-2的表达,但减少了基质金属蛋白酶-2,从而抑制了细胞的迁移和侵袭能力。这些结果强调了BRG1在乳腺癌发病机制中的重要性,BRG1可能作为一种预后标志物和潜在的选择性治疗靶点。
BRG1, a core component of the SWI/SNF chromatin-remodeling complex, has been implicated in cancer development; however, the biological significance of BRG1 in breast cancer remains unknown. We explored the role of BRG1 in human breast cancer pathogenesis. Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 437 breast cancer specimens and investigated its role in breast cancer cell proliferation, migration and invasion. Our Kaplan-Meier survival curves showed that high BRG1 expression is inversely correlated with both overall (P = 0.000) and disease-specific (P = 0.000) 5-year patient survival. Furthermore, we found that knockdown of BRG1 by RNA interference markedly inhibits cell proliferation and causes cessation of cell cycle. This reduced cell proliferation is due to G1 phase arrest as cyclin D1 and cyclin E are diminished whereas p27 is upregulated. Moreover, BRG1 depletion induces the expression of TIMP-2 but reduces MMP-2, thereby inhibiting the ability of cells to migrate and to invade. These results highlight the importance of BRG1 in breast cancer pathogenesis and BRG1 may serve as a prognostic marker as well as a potentially selective therapeutic target.
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