Evidence for a potential tumor suppressor role for the Na,K-ATPase ß1-subunit

Landon J. Inge, Sigrid A. Rajasekaran, Koji Yoshimoto, Paul S. Mischel, William McBride, Elliot Landaw, Ayyappan K. Rajasekaran

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

The Na,K-ATPase, consisting of two essential subunits (a, ß), plays a critical role in the regulation of ion homeostasis in mammalian cells. Recent studies indicate that reduced expression of the ß1 isoform (NaK-ß1) is commonly observed in carcinoma and is associated with events involved in cancer progression. In this study, we present evidence that repletion of NaK-ß1 in Moloney sarcoma virustransformed Madin-Darby canine kidney cells (MSVMDCK), a highly tumorigenic cell line, inhibits anchorage independent growth and suppresses tumor formation in immunocompromised mice. Additionally, using an in vitro cell-cell aggregation assay, we showed that cell aggregates of NaK-ß1 subunit expressing MSVMDCK cells have reduced extracellular regulated kinase (ERK) 1/2 activity compared with parental MSV-MDCK cells. Finally, using immunohistochemistry and fully quantitative image analysis approaches, we showed that the levels of phosphorylated ERK 1/2 are inversely correlated to the NaK-ß1 levels in the tumors. These findings reveal for the first time that NaK-ß1 has a potential tumor-suppressor function in epithelial cells.

Original languageEnglish
Pages (from-to)459-467
Number of pages9
JournalHistology and histopathology
Volume23
Issue number4
Publication statusPublished - Apr 2008

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology

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