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.
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February 2005
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Conference Article|
February 01 2005
Acquired glucose sensitivity of k-ras transformed fibroblasts
F. Chiaradonna;
F. Chiaradonna
1Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
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C. Magnani;
C. Magnani
1Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
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E. Sacco;
E. Sacco
1Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
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R. Manzoni;
R. Manzoni
1Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
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L. Alberghina;
L. Alberghina
1Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
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M. Vanoni
M. Vanoni
1
1Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy
1To whom correspondence should be addressed (email marco.vanoni@unimib.it).
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Publisher: Portland Press Ltd
Received:
November 05 2004
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2005 The Biochemical Society
2005
Biochem Soc Trans (2005) 33 (1): 297–299.
Article history
Received:
November 05 2004
Citation
F. Chiaradonna, C. Magnani, E. Sacco, R. Manzoni, L. Alberghina, M. Vanoni; Acquired glucose sensitivity of k-ras transformed fibroblasts. Biochem Soc Trans 1 February 2005; 33 (1): 297–299. doi: https://doi.org/10.1042/BST0330297
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