The plasma membrane calcium ATPase (PMCA) in colon cancer

The plasma membrane calcium ATPase (PMCA) is one of the most important calcium transporters in cells and is responsible for maintaining calcium homeostasis. Lack of differentiation is prominent in colon cancer and the induction of differentiation in vitro in cancer cells is associated with changes in calcium homeostasis. We observed an increase in the expression of PMCA4 mRNA and protein in HT-29 colon cancer cells during sodium butyrate and spontaneous confluency-induced differentiation. In contrast, no significant changes occurred in the expression of the PMCA1 isoform expression. At the tissue level, reduced expression of plasma membrane calcium ATPases were detected in three out of five colon cancer clinical samples compared to adjacent normal tissue samples; this indicates that the down-regulation of PMCA may be associated with dedifferentiation in colon cancer. To further understand the role of PMCA4 in regulating differentiation in colon cancers, PMCA4 expression was knocked down using small interfering RNA (siRNA) in HT-29 cells and the functional consequences of PMCA4 knockdown investigated. Our studies suggest that there are isoform specific changes in PMCA expression during differentiation in colon cancer cells and that PMCA4 may have a specific role in cells from the gastrointestinal trac