MTDH Mediates Estrogen-Independent Growth and Tamoxifen Resistance by Down-Regulating PTEN in MCF-7 Breast Cancer Cells
MTDH Mediates Estrogen-Independent Growth and Tamoxifen Resistance by Down-Regulating PTEN in MCF-7 Breast Cancer Cells
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MTDH 通过下调 MCF-7 乳腺癌细胞中的 PTEN 介导雌激素依赖性生长和他莫昔芬耐药性
DOI：
10.1159/000358719
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Yang, Qifeng
中科院分区：
文献类型：
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作者：
Xu, Chunyuan;Kong, Xiaoli;Yang, Qifeng
背景：约70%的人乳腺癌表达雌激素受体α (ER α)，雌激素在这类乳腺癌中起重要作用。据报道，雌激素独立生长可促进对选择性雌激素受体调节剂（SERMs）他莫昔芬（tamoxifen）的耐药性，而这种药物在临床上是ER α阳性乳腺癌患者的一线治疗药物。他莫昔芬的耐药性是乳腺癌临床治疗中的一个主要问题。方法：采用异位表达MDTH的MCF-7细胞。通过MTT、克隆形成和裸鼠肿瘤形成的方法证实MTDH在不依赖雌激素生长和他莫昔芬耐药中的作用。采用流式细胞术、western blot和siRNA技术研究其具体机制。结果：我们发现MTDH可以介导ER α阳性乳腺癌细胞的不依赖雌激素的生长并诱导对他莫昔芬的耐药。MTDH可降低PTEN的表达，上调AKT和BCL2的表达，抑制他莫昔芬诱导的细胞凋亡。结论：我们的研究表明MTDH是预测他莫昔芬临床疗效的候选标志物，靶向MTDH可以克服乳腺癌细胞对他莫昔芬的耐药。巴塞尔S. Karger股份有限公司版权所有
Background: About 70% of human breast cancers express estrogen receptor alpha (ER alpha) and in this kind of breast cancer estrogen plays an important role. Estrogen independent growth has been reported to promote resistance to one of the selective estrogen receptor modulators (SERMs) tamoxifen which is clinically the first line treatment for patients with ER alpha-positive breast cancer. The resistance of tamoxifen is a major problem in the clinical management of breast cancer. Methods: We used MCF-7 cells with ectopic expression of MDTH in this study. MTT, clone formation and tumor formation in nude mice methods were utilized to confirm the role of MTDH in estrogen-independent growth and tamoxifen resistance. Flow cytometry, western blot and siRNA were used to study the detailed mechanisms. Results: We found that MTDH could mediate estrogen-independent growth and induce resistance to tamoxifen in ER alpha-positive breast cancer cells. MTDH could reduce the expression of PTEN, up-regulate AKT and BCL2 and inhibit the apoptosis induced by tamoxifen. Conclusion: Our study indicated that MTDH was a candidate marker to predict the clinical efficacy of tamoxifen and targeting MTDH would overcome the resistance to tamoxifen in breast cancer cells. Copyright (C) 2014 S. Karger AG, Basel