Changes in the expression levels of Na⁺, K⁺-ATPase α-isoforms in colorectal cancer

Abstract

The catalytic subunit of Na⁺, K⁺-ATPase shows at least four isoforms, α1, α2, α3 and α4, each derived from a distinct gene. Here, we investigated expression levels of mRNA and protein of Na⁺, K⁺-ATPase α-isoforms in the human colorectal cancer mucosa and the normal mucosa. The specimens were obtained from surgical resection of patients in accordance with the recommendations of the Declaration of Helsinki. Informed consents were obtained from the patients at Toyama Medical and Pharmaceutical University Hospital. First, we examined the protein expression level of α1-isoform by using specific antibodies. Interestingly, decrease in the expression of α1-isoform was observed in all the cancer mucosae compared with the normal mucosae. But ouabain (5 μM)-sensitive Na⁺, K⁺-ATPase activities in both cancer and normal musosae were not significantly different. Real-time PCR (TaqMan) assay showed that the mRNA expression of α2- and α4-isoforms decreased in almost all the cancer mucosae. Interestingly, the expression level of the α3-isoform in the cancer mucosa was higher than that of the normal mucosa. These results suggest that decrease in protein expression of α1-isoform and increase in that of α3-isoform may be associated with colorectal cancers. [Jpn J Physiol 54 Suppl:S79 (2004)]