Inhibition of the transient receptor potential melastatin-2 channel causes increased DNA damage and decreased proliferation in breast adenocarcinoma cells.
Inhibition of the transient receptor potential melastatin-2 channel causes increased DNA damage and decreased proliferation in breast adenocarcinoma cells.
复制标题
DOI：
10.3892/ijo.2015.2919
复制
发表时间：
2015-05
影响因子：
5.2
通讯作者：
Koh DW
中科院分区：
文献类型：
--
作者：
Hopkins MM;Feng X;Liu M;Parker LP;Koh DW
瞬时受体电位melastatin-2（TRPM 2）是一种质膜阳离子通道，在感觉功能和促进细胞死亡中具有重要作用。然而，我们在这里证明，TRPM 2存在于MCF-7和MDA-MB-231人乳腺癌细胞的细胞核中，其药理学抑制或RNAi沉默导致细胞增殖降低。在非癌性HMEC和MCF-10A人乳腺上皮细胞中，既没有观察到对增殖的影响，也没有观察到TRPM 2在细胞核中的定位。对TRPM 2在细胞核中功能的可能影响的研究表明，与同等处理后的非癌乳腺细胞相比，MCF-7和MDA-MB-231人乳腺癌细胞中TRPM 2的药理学抑制或RNAi沉默导致DNA损伤水平增加高达4倍。这些结果表明，TRPM 2在人乳腺癌细胞中具有一种新的核功能，可促进基因组DNA的完整性，这一发现与其先前报道的在非癌细胞中作为质膜阳离子通道的作用不同。总之，我们在这里报告了TRPM 2促进的一种新效应，它的功能是最大限度地减少DNA损伤，因此可能在保护乳腺癌细胞中的基因组DNA中发挥作用。因此，我们的研究提供了令人信服的证据，证明TRPM 2在乳腺癌细胞中具有独特的作用。因此，这些研究表明，TRPM 2是一个潜在的治疗靶点，其药理学抑制可能提供一种创新的策略，以选择性地增加乳腺癌细胞中的DNA损伤水平。
Transient receptor potential, melastatin-2 (TRPM2) is a plasma membrane cation channel with important roles in sensory functions and promoting cell death. However, we demonstrated here that TRPM2 was present in the nuclei of MCF-7 and MDA-MB-231 human breast adenocarcinoma cells, and its pharmacologic inhibition or RNAi silencing caused decreased cell proliferation. Neither an effect on proliferation nor a localization of TRPM2 in the nucleus was observed in noncancerous HMEC and MCF-10A human mammary epithelial cells. Investigation of possible effects of TRPM2 function in the nucleus demonstrated that pharmacologic inhibition or RNAi silencing of TRPM2 in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells caused up to 4-fold increases in DNA damage levels, as compared to noncancerous breast cells after equivalent treatments. These results indicate that TRPM2 has a novel nuclear function in human breast adenocarcinoma cells that facilitates the integrity of genomic DNA, a finding that is distinct from its previously reported role as a plasma membrane cation channel in noncancerous cells. In summary, we report here a novel effect promoted by TRPM2, where it functions to minimize DNA damage and thus may have a role in the protection of genomic DNA in breast cancer cells. Our study therefore provides compelling evidence that TRPM2 has a unique role in breast adenocarcinoma cells. Accordingly, these studies suggest that TRPM2 is a potential therapeutic target, where its pharmacologic inhibition may provide an innovative strategy to selectively increase DNA damage levels in breast cancer cells.
登录
查看更多内容
影响因子：
4.8
作者：
Zeng, X.;Sikka, S. C.;Huang, L.;Sun, C.;Xu, C.;Jia, D.;Abdel-Mageed, A. B.;Pottle, J. E.;Taylor, J. T.;Li, M.
通讯作者：
Li, M.
TRPM8离子通道的药理阻滞改变了小鼠的冷疼痛反应。
影响因子：
3.7
作者：
Knowlton WM;Daniels RL;Palkar R;McCoy DD;McKemy DD
通讯作者：
McKemy DD
影响因子：
16
作者：
Hara, Y;Wakamori, M;Mori, Y
通讯作者：
Mori, Y
影响因子：
8
作者：
Blenn, C.;Wyrsch, P.;Bader, J.;Bollhalder, M.;Althaus, Felix R.
通讯作者：
Althaus, Felix R.
影响因子：
5.5
作者：
Bessac, Bret F.;Fleig, Andrea
通讯作者：
Fleig, Andrea