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Forschungsdatenbank PMU-SQQUID

Modification of cellular ion transport by the Ha-ras oncogene: Steps towards malignant transformation
Ritter, M; Woll, E
CELL PHYSIOL BIOCHEM. 1996; 6(5): 245-270.
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PMU-Autor/inn/en

Ritter Markus

Abstract

Expression of the transforming Ha-ras oncogene in NIH 3T3 fibroblasts (+ras cells) results in growth-factor-independent proliferation, breakdown of actin stress fiber network and increase in intracellular pH and cell volume due to activation of the Na+/H+ exchanger and Na+, K+, 2Cl(-) cotransport. +ras cells respond to mitogens like serum or bradykinin with sustained oscillations of the cell membrane potential due to stimulated calcium entry which triggers pulsatile release of calcium from internal stores and subsequent activation of calcium-sensitive K+ channels. Calcium antagonists like bepridil or nifedipine inhibit cellular calcium entry and oscillations of the intracellular calcium concentration, protect +ras cells against actin stress fiber depolymerization, block activation of the Na+/H+ exchanger and inhibit cell proliferation. Inhibition of the Na+/H+ exchanger inhibits the increase in the intracellular pH and cell proliferation but does not alter cytoskeletal rearrangement, calcium entry or oscillations of intracellular calcium. In cells not expressing the oncogene (-ras cells), bradykinin causes a single transient hyperpolarization, is without effect on cytoarchitecture and leads to cell shrinkage unless actin filament disruption is induced by cytochalasin D or pretreatment of the cells with LiCl. Apparently the oscillations of intracellular calcium are required for depolymerization of the actin filaments and for activation of the Na+/H+ exchanger. Thus the alterations of ion transport are prerequisites for growth-factor-independent proliferation of Ha-ras-oncogene-expressing cells.


Find related publications in this database (Keywords)

ras oncogene
intracellular calcium
calcium oscillations
intracellular pH
Na+/H+ exchanger
cell volume
ion channels
actin cytoskeleton