Thesis
Transient receptor potential melastatin-2 (TRPM2) channel in breast cancer cells: unique localization and cellular role
Washington State University
Master of Science (MS), Washington State University
2013
Handle:
https://hdl.handle.net/2376/101670
Abstract
Transient receptor potential melastatin-2 (TRPM2) channel is a non-selective cation channel that is widely expressed throughout the body. It has been shown to be associated with cancer progression, neurodegenerative disorders, inflammatory responses, and diabetes. Here, we assessed the role of TRPM2 in breast cells. We showed that the subcellular localization of TRPM2 is remarkably different in cancerous and noncancerous breast cells. In MCF-10A cells (noncancerous), TRPM2 protein is located outside of the nucleus, whereas in MCF-7 and MDA-MB-231 cells (cancerous), a portion of the TRPM2 protein can be detected in the nucleus. We also found that TRPM2 inhibitors decrease the proliferation of MCF-7 cells. In addition, the inhibitors potentiate the cytotoxic effects of chemotherapeutic agents in cancer cells, but decrease these effects in normal cells. Furthermore, we have found that silencing of TRPM2 down-regulates nuclear poly(ADP-ribosyl)ation by suppressing poly(ADP-ribose) polymerase-1 (PARP-1) in breast cancer cells, but up-regulates it in noncancerous cells. Finally, we revealed a previously undiscovered function of v TRPM2 in maintaining NAD+ levels in noncancerous cells. We conclude that inhibiting TRPM2 in breast cancer cells may be a potential strategy for the selective treatment of breast cancer.
Metrics
3 File views/ downloads
12 Record Views
Details
- Title
- Transient receptor potential melastatin-2 (TRPM2) channel in breast cancer cells
- Creators
- Mengwei Liu
- Contributors
- Kathryn E. Meier (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Pharmacy and Pharmaceutical Sciences, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Identifiers
- 99900525062601842
- Language
- English
- Resource Type
- Thesis