Evidence that TRPM7 is required for breast cancer cell proliferation
Evidence that TRPM7 is required for breast cancer cell proliferation
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DOI：
10.1152/ajpcell.00624.2008
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发表时间：
2009-09-01
影响因子：
5.5
通讯作者：
Ouadid-Ahidouch, Halima
中科院分区：
文献类型：
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作者：
Guilbert, Arnaud;Gautier, Mathieu;Ouadid-Ahidouch, Halima
Guilbert A、Gautier M、Dhennin-Duthille I、Haren N、Sevestre H、Ouadid-Ahidouch H。TRPM7 是乳腺癌细胞增殖所必需的证据。 Am J Physiol Cell Physiol 297：C493-C502，2009。首次发表于 2009 年 6 月 10 日； doi:10.1152/ajpcell.00624.2008.-由于瞬时受体电位 (TRP) 通道与肿瘤进展有关，因此我们研究了 TRPM7 通道在乳腺癌细胞增殖中的潜在作用。在全细胞膜片钳下，在 MCF-7 细胞中观察到 Mg2+ 抑制的阳离子 (MIC) 电流。该电流的特征是内向电流和强外向整流电流，这两种电流均受到细胞内 Mg2+ 或 Mg2+-ATP 的存在以浓度依赖性方式抑制。 La3+ 减少内向电流，而外向电流对 2-氨基乙氧基二苯硼酸盐 (2-APB)、精胺、La3+ 和氟芬那酸敏感。重要的是，在人乳腺癌上皮细胞 (hBCE) 的原代培养物中也记录了类似的 MIC 电流。此外，在 hBCE 和 MCF-7 细胞中都发现了 TRPM7 转录本。在MCF-7细胞中，TRPM7小干扰RNA抑制MIC电流。有趣的是，我们发现MCF-7细胞中TRPM7沉默也降低了细胞增殖和细胞内Ca2+浓度。 TRPM7 通道也在人类乳腺癌和健康组织中被发现。重要的是，TRPM7 通道在与重要的 Ki67 或肿瘤大小相关的 III 级乳腺癌样本中过度表达。我们的研究结果强烈表明 TRPM7 可能通过调节 Ca2+ 内流参与乳腺癌细胞的增殖潜力。
Guilbert A, Gautier M, Dhennin-Duthille I, Haren N, Sevestre H, Ouadid-Ahidouch H. Evidence that TRPM7 is required for breast cancer cell proliferation. Am J Physiol Cell Physiol 297: C493-C502, 2009. First published June 10, 2009; doi:10.1152/ajpcell.00624.2008.-Because transient receptor potential (TRP) channels have been implicated in tumor progression, we have investigated the potential role of TRPM7 channel in breast cancer cell proliferation. Under whole cell patch clamp, a Mg2+-inhibited cationic (MIC) current was observed in MCF-7 cells. This current was characterized by an inward current and a strong outward rectifying current that were both inhibited in a concentration-dependent manner by the presence of intracellular Mg2+ or Mg2+-ATP. The inward current was reduced by La3+, and the outward current was sensitive to 2-aminoethoxydiphenyl borate (2-APB), spermine, La3+, and flufenamic acid. Importantly, a similar MIC current was also recorded in the primary culture of human breast cancerous epithelial cells (hBCE). Moreover, TRPM7 transcripts were found in both hBCE and MCF-7 cells. In MCF-7 cells, the MIC current was inhibited by TRPM7 small interfering RNA. Interestingly, we found that cell proliferation and intracellular Ca2+ concentration were also reduced by TRPM7 silencing in MCF-7 cells. TRPM7 channels were also found in both human breast cancer and healthy tissues. Importantly, TRPM7 channel was overexpressed in grade III breast cancer samples associated with important Ki67 or tumor size. Our findings strongly suggest that TRPM7 is involved in the proliferative potentiality of breast cancer cells, probably by regulating Ca2+ influx.