The Journal of Membrane Biology, 2011, 242(2):53-67.

The Life and Death of Breast Cancer Cells: Proposing a Role for the Effects of Phytoestrogens on Potassium Channels

Joanne L. Wallace, Iain F.Gow, Mary Warnock

School of Health Sciences, Queen Margaret University, Musselburgh, Edinburgh, Scotland, UK

Changes in the regulation of potassium channels are increasingly implicated in the altered activity of breast cancer cells. Increased or reduced expression of a number of K(+) channels have been identified in numerous breast cancer cell lines and cancerous tissue biopsy samples, compared to normal tissue, and are associated with tumor formation and spread, enhanced levels of proliferation, and resistance to apoptotic stimuli. Through knockout or silencing of K(+) channel genes, and use of specific or more broad pharmacologic K(+) channel blockers, the growth of numerous cell lines, including breast cancer cells, has been modified. In this manner it has been proposed that in MCF7 breast cancer cells proliferation appears to be regulated by the activity of a number of K(+) channels, including the Ca(2+) activated K(+) channels, and the voltage-gated K(+) channels hEAG and K(v)1.1. The effect of phytoestrogens on K(+) channels has not been extensively studied but yields some interesting results. In a number of cell lines the phytoestrogen genistein inhibits K(+) current through several channels including K(v)1.3 and hERG. Where it has been used, structurally similar daidzein has little or no effect on K(+) channel activity. Since many K(+) channels have roles in proliferation and apoptosis in breast cancer cells, the impact of K(+) channel regulation by phytoestrogens is of potentially great relevance.

美国《膜生物学杂志》，2011年7月

乳腺癌细胞的生与死︰ 提出植物雌激素对钾离子通道的影响

乔安妮 L. 华莱士，伊恩 F. 高，玛丽  沃诺克

英国苏格兰玛格丽特女王大学健康科学学院

钾离子通道调节的变化会逐渐引起乳腺癌细胞活性的改变。与正常组织相比，增加或减少一定K（+） 通道数目的表达已在众多的乳腺癌细胞和癌组织活检标本中被确认，与肿瘤的形成和扩散有关，提高细胞增殖的水平并且抵抗细胞凋亡的外界因素。通过基因敲除或静默K （+） 通道基因，并且使用特殊的或更广泛的药理K（+） 通道阻滞剂，众多细胞的生长，包括乳腺癌细胞等被更正。以这种方式提出在 MCF7 乳腺癌细胞中细胞增殖似乎受到K （+） 通道的调节，包括 Ca(2+)激活的，并且电压门控了K （+） 通道 hEAG 和 K (v) 1.1。植物雌激素对K （+） 通道的影响尚未广泛研究，但是已经产生了一些有趣的结果。在大量的细胞中，植物雌激素金雀异黄素抑制了K （+） 电流通过几条渠道包括 K (v) 1.3 和 hERG。在使用时，结构类似的大豆苷元却对K （+） 通道活动很少或几乎没有影响。由于在乳腺癌细胞中许多K（+） 通道对于细胞增殖及凋亡中起到作用，植物雌激素对K （+） 通道调节的影响可能具有重大意义。