Inhibition of the transient receptor potential melastatin-2 channel causes increased DNA damage and decreased proliferation in breast adenocarcinoma cells

International Journal of Oncology
Mandi M HopkinsDavid W Koh

Abstract

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 pro...Continue Reading

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Citations

Jun 8, 2018·Pharmaceuticals·Aline Hantute-GhesquierV'yacheslav Lehen'kyi
May 16, 2019·Cold Spring Harbor Perspectives in Biology·Sarah J Roberts-ThomsonGregory R Monteith
Oct 28, 2019·Current Molecular Pharmacology·Melvin N RosalezMarvin A Soriano-Ursúa
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Jun 9, 2021·Cell Death & Disease·Rui LinBaomin Shi
May 24, 2019·Medical Cannabis and Cannabinoids·Petra Luschnig, Rudolf Schicho

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Datasets Mentioned

BETA
MDA-MB-231

Methods Mentioned

BETA
Assay
electrophoresis
scraping
Protein Assay

Software Mentioned

Gen5
Axiovision
CometScore
Quantity One

Related Concepts