Oncogene Ras and Mitochondrial activity

Author: L. Alberghina
Submitted: Thursday 10th of February 2011 10:11:04 AM
Submitted by: egf
Language: English
Content type: Learning resource
Educational levels: expert, qc3

Abstract

Complex cellular functions are often determined by the dynamic interactions occurring in networks of hundreds or thousands gene products that generate system-level properties largely unpredictable considering only the behaviour of individual nodes of the network. The phenotype of “in vitro” growing cancer cells is thus going to be considered as an integration of system-level properties, whose underlying network are analyzed by genome-wide and hypothesis driven experiments under various nutrients perturbations. The following results have been obtained: low glucose reduces proliferation of transformed cells and enhances their death; low glutamine reduces proliferation of transformed cells and arrest them in S phase; signalling pathways relevant for cell proliferation are differentially affected by nutrient perturbations in normal and transformed cells; transformed cells as compared to normal ones present: enhanced glycolysis; increased mitochondrial potential; altered mitochondrial fusion/fission; reduced amounts and activity of mitochondrial Complex I; cAMP/PKA pathway is down-regulated in many cancer cell lines; stimulation of PKA pathway by forskolin slightly inhibits normal cell proliferation, protects transformed cells from low glucose induced cell death, enhances mitochondrial activity and stimulates Complex I activity and expression; metabolome analysis performed with stable isotope labelling of glucose and glutamine indicate that transformed cells undergo metabolic remodelling that involves glycolysis and mitochondrial metabolism of glucose and glutamine derived products. The above findings are discussed in a systems biology approach.

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abstract alberghina_5121.pdf

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Citation

L. Alberghina. Oncogene Ras and Mitochondrial activity. EUROGENE portal. February 2011. online: http://eurogene.open.ac.uk/content/oncogene-ras-and-mitochondrial-activity

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