THE VITAL ROLE OF TRPM2 IN BREAST CANCER CELL PROLIFERATION AND ITS DIFFERENCE IN EXPRESSION BETWEEN NON-HISPANIC WHITE AND NON-HISPANIC BLACK FEMALES

Objective: To study the racial disparity of transient receptor potential melastatin-related channel subtype 2 (TRPM2) expression in non-Hispanic black (NHB) women and non-Hispanic white women (NHW) breast cancer tissues. Specific roles of TRPM2 in the proliferation and apoptosis of the human mitogenic breast cancer cells (MCF-7 ER+) are also investigated. Materials and Methods: TRPM2 expression analysis was performed using the normalized mRNA expression data downloaded from Broad GDAC Firehose. The functions of TRPM2 in normal and cancer cells are revealed using patch-clamp recording and intracellular calcium imaging techniques. Results: TRPM2 is expressed at different levels in breast ductal and lobular neoplasm disease between NHB and NHW. Selective knock-down of TRPM2 mRNA with small interfering RNA (siRNA/TRPM2) caused substantial inhibition of cell proliferation of MCF-7(ER+) cells but not in the control human mammary epithelial (HME) cells. The siRNA/TRPM2 also induced cellular apoptosis in MCF-7(ER+) cells but not HME cells. Immunofluorescent staining shows that TRPM2 abnormally localizes in the MCF-7(ER+) nuclei but not HME cells. Conclusions: These results suggest that TRPM2 is essential in promoting MCF-7(ER+) cell proliferation and may be a potential target for breast cancer treatment.