Dynamic function of secretory pathway Ca2+‐ATPase 2 (SPCA2) and transient receptor potential (TRP) channels in breast cancer

Ca 2+ is a vital second messenger critical in regulating cellular proliferation and apoptosis. Intracellular Ca 2+ concentrations are tightly regulated on multiple levels by various channels and pumps present in the plasma membrane, ER and Golgi. One such pump is the secretory pathway Ca 2+ ‐ATPase SPCA2, which is part of a dynamic system that allows for efficient transcellular transport of Ca 2+ into milk. Negative alteration of this system leads to abnormal Ca 2+ homeostasis, and a strong correlation has formed with a negative prognosis for breast cancer. In this project, we explored a variety of transient receptor potential (TRP) channels suspected of interacting downstream of SPCA2. Using a mammary carcinoma cell line, T47D, we performed molecular (RT‐PCR) techniques to assess channel expression and consequently knockdown, by lentiviral delivery of shRNA, all notably upregulated ion channels (Orai1, TRPC4, TRPC6, and TRPV6). Following successful knockdown, we will assess cell proliferation and tumorigenesis. Our study should shed considerable light on the role that Ca 2+ ion channels play in breast carcinogenesis, and elucidate a possible drug target for breast cancer treatment. Supported by NIH grant GM 62142