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首页> 外文期刊>Journal of Pathology: Journal of the Pathological Society of Great Britain and Ireland >Over-expression of metallothionein predicts chemoresistance in breast cancer.
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Over-expression of metallothionein predicts chemoresistance in breast cancer.

机译：金属硫蛋白的过度表达预示着乳腺癌的化学耐药性。

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摘要

Metallothionein (MT) plays a role in fundamental cellular processes such as proliferation, apoptosis and differentiation. We examined MT expression in women with invasive breast ductal carcinoma who underwent mastectomy/lumpectomy without neo-adjuvant treatment. We showed that MT was over-expressed in 87.9% of breast cancer tissues examined, with the mean percentage of positive cells at 30%. There were two patterns of MT expression: predominantly cytoplasmic in 75.9% and nuclear in 24.1% of MT-positive cases. Higher MT scores were associated with poorer histological grade (p = 0.009) but were independent of age, tumour size and oestrogen receptor status. For patients who were treated with adjuvant chemotherapy (cyclophosphamide/methotrexate/5 fluorouracil- or doxorubicin-based regimes), those with high MT expression had a significantly lower recurrence-free survival (p = 0.048), suggesting a role of MT in predicting disease recurrence. Down-regulation of MT in MCF-7 cells by silencing the MT-2A gene (the most abundantly expressed of the 10 known functional MT isoforms) increased chemosensitivity of the cells to doxorubicin. To examine the mechanisms underlying these clinical data, we used siRNAs to decrease MT-2A mRNA expression and protein expression. In MT down-regulated cells challenged with the IC(50) concentration of doxorubicin, we observed a significant reduction in cell viability. Cell cycle analysis also revealed a corresponding increase in apoptosis in the MT down-regulated cells following doxorubicin exposure, showing that down-regulation of MT increased susceptibility to doxorubicin cytotoxicity. The data suggest that MT could be a potential marker of chemoresistance and a molecular therapeutic target.
机译：金属硫蛋白（MT）在基本的细胞过程中起作用，例如增殖，凋亡和分化。我们检查了接受乳腺切除/肿块切除术而未接受新辅助治疗的浸润性乳腺导管癌女性的MT表达。我们显示，MT在被检查的87.9％的乳腺癌组织中过表达，阳性细胞的平均百分比为30％。 MT的表达有两种模式：在MT阳性病例中，主要是细胞质，占75.9％，在核中占24.1％。较高的MT评分与较差的组织学分级相关（p = 0.009），但与年龄，肿瘤大小和雌激素受体状态无关。对于接受辅助化疗（基于环磷酰胺/甲氨蝶呤/ 5氟尿嘧啶或阿霉素的方案）的患者，MT表达高的患者无复发生存率明显降低（p = 0.048），表明MT在预测疾病中的作用复发。通过沉默MT-2A基因（在10种已知功能性MT同工型中表达最丰富），MCF-7细胞中MT的下调增加了细胞对阿霉素的化学敏感性。为了检查这些临床数据的潜在机制，我们使用了siRNA来降低MT-2A mRNA表达和蛋白质表达。在MT下调的细胞受到IC（50）浓度的阿霉素的挑战，我们观察到细胞活力的显着降低。细胞周期分析还显示，阿霉素暴露后，MT下调的细胞凋亡相应增加，表明MT下调增加了对阿霉素细胞毒性的敏感性。数据表明MT可能是化学耐药性的潜在标志物和分子治疗靶标。

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