Acquired glucose sensitivity of k-ras transformed fibroblasts. (1st February 2005)

• Record Type: Journal Article
• Authors: Chiaradonna, F.; Magnani, C.; Sacco, E.; Manzoni, R.; Alberghina, L.; Vanoni, M.
• Is Part Of: Biochemical Society transactions. Volume 33:Number 1(2005)
• Page Start: 297
• Page End: 299
• Publication Date: 2005-02-01
• Subjects: apoptosis -- fragility -- glucose sensitivity -- MAPK -- Ras -- transformed cells -- transformed fibroblasts; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0330297
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : 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 RasGTP, 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.