Molecular deficiency (ies) in MT₁ melatonin signaling pathway underlies the melatonin-unresponsive phenotype in MDA-MB-231 human breast cancer cells.
Molecular deficiency (ies) in MT₁ melatonin signaling pathway underlies the melatonin-unresponsive phenotype in MDA-MB-231 human breast cancer cells.
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DOI：
10.1111/jpi.12117
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发表时间：
2014-04
影响因子：
10.3
通讯作者：
Hill SM
中科院分区：
文献类型：
--
作者：
Mao L;Yuan L;Xiang S;Zeringue SB;Dauchy RT;Blask DE;Hauch A;Hill SM
褪黑激素已在体外和体内多次被证明可以抑制人类乳腺肿瘤细胞的生长。其抗增殖作用已在 MCF-7 人乳腺癌细胞和其他几种雌激素受体 α (ERα) 阳性人乳腺癌细胞系中得到充分研究。然而，MDA-MB-231乳腺癌细胞系（一种广泛用于乳腺癌研究的ERα阴性细胞系）已被证明在体外对褪黑激素的生长抑制作用没有反应。在这里，我们检查了褪黑激素对几种 ERα 阴性乳腺癌细胞系（包括 MDA-MB-231、BT-20 和 SK-BR-3 细胞）细胞增殖的影响。尽管 MT1 G 蛋白偶联受体在所有三种细胞系中都有表达，但褪黑激素显着抑制 SK-BR-3 细胞的增殖，而对 MDA-MB-231 和 BT-20 细胞的生长没有任何显着影响。我们证实 MT1 相关 Gα 蛋白在 MDA-MB-231 细胞中表达。进一步的研究表明，MDA-MB-231 细胞中褪黑激素无反应可能是由 Gαi 蛋白下游信号传导异常引起的，导致 ERK1/2 活性的差异调节。
Melatonin, has been shown repeatedly to inhibit the growth of human breast tumor cells in vitro and in vivo. Its anti-proliferative effects have been well-studied in MCF-7 human breast cancer cells and several other estrogen receptor α (ERα)-positive human breast cancer cell lines. However, the MDA-MB-231 breast cancer cell line, an ERα negative cell line widely used in breast cancer research, has been shown to be unresponsive to melatonin’s growth-suppressive effect in vitro. Here we examined the effect of melatonin on the cell proliferation of several ERα-negative breast cancer cell lines including MDA-MB-231, BT-20 and SK-BR-3 cells. Although the MT1 G-protein-coupled receptor is expressed in all three cell lines, melatonin significantly suppressed the proliferation of SK-BR-3 cells without having any significant effect on the growth of MDA-MB-231 and BT-20 cells. We confirmed that the MT1-associated Gα proteins are expressed in MDA-MB-231 cells. Further studies demonstrated that the melatonin-unresponsiveness in MDA-MB-231 cells may be caused by aberrant signaling downstream of the Gαi proteins, resulting in differential regulation of ERK1/2 activity.