Evidence for a potential tumor suppressor role for the Na,K-ATPase beta1-subunit

Histol Histopathol. 2008 Apr;23(4):459-67. doi: 10.14670/HH-23.459.


The Na,K-ATPase, consisting of two essential subunits (alpha, beta), plays a critical role in the regulation of ion homeostasis in mammalian cells. Recent studies indicate that reduced expression of the beta1 isoform (NaK-beta1) is commonly observed in carcinoma and is associated with events involved in cancer progression. In this study, we present evidence that repletion of NaK-beta1 in Moloney sarcoma virus-transformed Madin-Darby canine kidney cells (MSV-MDCK), 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-beta1 subunit expressing MSV-MDCK 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-beta1 levels in the tumors. These findings reveal for the first time that NaK-beta1 has a potential tumor-suppressor function in epithelial cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Line, Transformed
  • Cell Transformation, Viral
  • Dogs
  • Immunohistochemistry
  • Kidney / cytology
  • Mice
  • Mice, SCID
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Moloney murine sarcoma virus / physiology
  • Phosphorylation
  • Protein Subunits / metabolism
  • Protein Subunits / physiology*
  • Sodium-Potassium-Exchanging ATPase / chemistry*
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Sodium-Potassium-Exchanging ATPase / physiology*
  • Time Factors
  • Transplantation, Heterologous
  • Tumor Burden
  • Tumor Suppressor Proteins / metabolism
  • Tumor Suppressor Proteins / physiology*
  • Xenograft Model Antitumor Assays


  • Protein Subunits
  • Tumor Suppressor Proteins
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Sodium-Potassium-Exchanging ATPase