Acquired glucose sensitivity of k-ras transformed fibroblasts.
Mutational activation of the ras gene is critical for the onset of different malignant phenotypes. We constructed a dominant negative mutant (GEF-DN) of a Ras activator protein (guanine nucleotide-exchange factor) that upon over-expression in k-ras transformed NIH 3T3 fibroblasts strongly reduces intracellular Ras*GTP, reverting these cells to wild-type phenotype for morphology, anchorage-independent growth and reduction of tumour formation in nude mice. Here we review evidence showing that the enhanced proliferation potential of NIH-ras cells requires high initial glucose concentration in the medium and sustained Ras pathway activation. The exquisite sensitivity of NIH-ras fibroblasts to a shortage in nutrient and energy supply highlights an acquired fragility of cancer cells that may be exploited for therapeutic purposes.
Chiaradonna
F
F
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
Magnani
C
C
Sacco
E
E
Manzoni
R
R
Alberghina
L
L
Vanoni
M
M
D000818:Animals; D002461:Cell Line, Transformed; D005347:Fibroblasts / Q000378:metabolism*; D011905:Genes, ras; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction
D005947:Glucose