Increase in ouabain-sensitive K+-ATPase activity in hepatocellular carcinoma by overexpression of Na+, K+-ATPase alpha 3-isoform.
Na(+),K(+)-ATPase is a housekeeping pump in virtually all animal cells. Recently, cardiac glycosides that inhibit Na(+),K(+)-ATPase have been reported to be candidate for novel anticancer drug. Here, we investigated clinical significance of Na(+),K(+)-ATPase alpha1-isoform (alpha 1NaK), alpha2-isoform (alpha 2NaK) and alpha 3-isoform (alpha 3NaK) in hepatocellular carcinoma (HCC). Interestingly, the expression levels of alpha 3NaK protein in HCC tissues were significantly higher than those in the accompanying non-tumor tissues, whereas no significant increases in expression of alpha 1NaK and alpha 2NaK proteins were observed in HCC compared to non-tumor tissues. The ouabain (10 microM)-sensitive K(+)-ATPase activities (Na(+),K(+)-ATPase activities) in the membrane fraction from HCC tissue were significantly higher than those from non-tumor tissues. The Na(+),K(+)-ATPase activity was positively and significantly correlated with the expression level of alpha 3NaK. Apparent affinity for Na(+) in the Na(+),K(+)-ATPase activity in HCC tissues was significantly lower than that in non-tumor tissues, consistent with an elevated expression of alpha 3NaK relative to alpha 1NaK. Our results suggest that overexpression of alpha 3NaK increases the Na(+),K(+)-ATPase activity of HCC cells.
Shibuya
Kazuto
K
Department of Surgery II, Toyama 930-0194, Japan.
Fukuoka
Junya
J
Fujii
Takuto
T
Shimoda
Eri
E
Shimizu
Takahiro
T
Sakai
Hideki
H
Tsukada
Kazuhiro
K
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D015854:Up-Regulation
D007527:Isoenzymes; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase