Na,K-ATPase is a ubiquitous transmembrane heterodimer that regulates and maintains the low intracellular Na+:K+ ratio necessary for cell homeostasis. Na,K-ATPase is composed of two non-covalently linked subunits, the catalytic and ligand-binding α-subunit and the β-subunit. It was previously shown that altered expression of the alpha and beta subunits results in drastic changes in the structure and functions of epithelial cells that are commonly observed in cancer cells. This suggests α- and β-subunit expression patterns may be a useful clinical prognosticator for cancer. Molecular tumor markers are valuable in prognostication, early tumor detection and in stratifying patients for treatment and follow-up regimens.

INNOVATION:  The present invention involves the use of Na,K-ATPase subunit protein expression patterns for predicting clinical outcomes in patients with RCC and TCC and possibly other carcinomas.

POTENTIAL APPLICATIONS 

• Predict recurrence of bladder cancer
• Identify patients for therapeutic decision making

STAGE OF DEVELOPMENT:  In a clinical outcome study, the UCLA researchers further examined protein expression of Na,K-ATPase in a histopathologically well-characterized group of more than 150 patients representing a wide spectrum of tumor grades and disease stages with transitional cell carcinoma (TCC). Expression patterns of Na,K-ATPase subunits, measured in urothelial tissue microarrays (TMA), were correlated with clinicopathological parameters and patient outcomes to determine their potential diagnostic values. Na,K-ATPase α and Na,K-ATPase β subunits were demonstrated to be better predictors of recurrence risk and recurrence time than either the stage or grade of the tumor.

Related Papers (Selected) Analysis of the Na,K-ATPase α and β-subunit expression profiles of the bladder cancer using tissue microarrays. Cancer 2003 Apr 15; 97(8):1859-68. more... Na,K-ATPase ß-Subunit Is Required for Epithelial Polarization, Supression of Invasion, and Cell Motility. Molecular Biology of the Cell. 12, 279-295. more... Reduced Expression of β-Subunit of Na,K-ATPase in Human Clear-Cell Renal Cell Carcinoma. Journal of Urology. 162, 574-580. more... Na,K-ATPase activity is required for formation of tight junctions, desmosomes, and induction of polarity in epithelial cells. Mol. Biol. Cell 12: 3717-3732. more...

Reference: UCLA Case Nos. 2002-207; 2005-607

PCT Publication Number: PCT/US03/10826