Interaction and Regulation of Calcium Homeostasis by TRPV Channels and SPCA2 in Breast Cancer

Abstract

Breast cancer is one of the most common forms of cancer in women, causing over 40,000 deaths per year. The major concern with breast cancer is its tendency to metastasize, preferentially, to the brain, bone and other areas of high physiological calcium. Calcium is a vital component of the breast, as mammary tissue has the ability to sequester and compartmentalize such calcium. During lactation, mammary cells are required to concentrate the 2mM blood concentration of milk into the 40-80mM concentration of calcium found in milk. This action requires a highly coordinated group of calcium channels and pumps to seize the calcium into intracellular storage compartments. We have shown in previous studies that SPCA2 is highly upregulated during lactation and tumorigenesis. Additional studies from others have shown that TRP channels are also upregulated in lactation and tumorigenesis. Here we show that this induction is due to the interaction of these two molecular components of calcium homeostasis in breast tissue.