Publication: Evidence for a potential tumor suppressor role for the Na,K-ATPase B1-subunit
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Date
2008
Authors
Inge, Landon J. ; Rajasekaran, Sigrid A. ; Yoshimoto, Koji ; Mischel, Paul S. ; McBride, William ; Landaw, Elliot ; Rajasekaran, Ayyappan K.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
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.
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