A35

The plasma membrane calcium ATPase (PMCA) is an important calcium transporter in all cells and plays a crucial role in maintaining low intracellular Ca2+ levels through the active transport of calcium across the plasma membrane. PMCA is encoded by 4 genes (PMCA1-4), with PMCA1 and 4 expressed in colon epithelial cells. In this study, we examined the expression of PMCA4 in human colon cancer tissue and surrounding normal tissue using real time RT-PCR, and we have observed significant reduction of PMCA4 mRNA in some colon cancers. This is consistent with our previous findings of increased PMCA4 mRNA transcription and protein expression in a human colon cancer cell line (HT-29) during differentiation. To evaluate the possible role of altered PMCA4 expression in colon cancer, small interfering RNA (siRNA) technology was used to silence PMCA4 gene expression in HT-29 cells and the functional consequences of PMCA4 knock down on calcium homeostasis was investigated. Our results suggest that alterations in PMCA4 are likely to have functional consequences on calcium homeostasis and cell signaling in colon cancer.

First AACR Centennial Conference on Translational Cancer Medicine-- Nov 4-8, 2007; Singapore