Calcium transport in the mammary gland: A role for secretory pathway calcium ATPase 2 (SPCA2) in normal physiology and breast cancer

Abstract

Intracellular calcium levels must be tightly controlled to maintain intracellular homeostasis; a process that is reliant on calcium transporters. One group of calcium transporters, the secretory pathway calcium ATPases (SPCAs), of which two isoforms have been identified, are involved in the transport of calcium and manganese ions across the Golgi apparatus membrane. We investigated the hypothesis that SPCAs, in particular the less widely expressed SPCA2, are important in mammary gland physiology and pathophysiology. We assessed the expression of both SPCA1 and SPCA2 in mammary glands isolated from virgin, pregnant, lactating and involuting mice and their localisation in tissue sections isolated from lactating mice. SPCA2 and SPCA1 mRNA levels were also assessed in a bank of tumorigenic and non-tumorigenic human breast epithelial cell lines and clinical breast cancer samples. We saw an increase in SPCA2 mRNA during lactation and also in the breast cancer derived cell lines compared to normal breast cell lines. We also observed an increase in SPCA2 mRNA in the clinical tumour samples compared to matched normal tissue. We are currently assessing the functional consequences of SPCA2 over-expression on global calcium regulation. These studies will further our understanding of the functional role of SPCA2 in lactation and the consequences of its up-regulation in breast cancer. Our results highlight the importance of SPCA2 in both normal mammary gland physiology and pathophysiology