2011
DOI: 10.2741/3814
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Death pathways triggered by activated Ras in cancer cells

Abstract: Ras GTPases are best known for their ability to serve as molecular switches regulating cell growth, differentiation and survival. Gene mutations that result in expression of constitutively active forms of Ras proteins have been clearly linked to oncogenesis in animal models and humans. However, over the past two decades, evidence has gradually accumulated to support a paradoxical role for Ras proteins in the initiation of cell death pathways. The balance between the opposing functions of Ras in cell proliferat… Show more

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Cited by 55 publications
(47 citation statements)
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References 213 publications
(248 reference statements)
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“…Paradoxically, Ras also regulates growth-inhibitory pathways such as apoptosis and senescence (5,50,51). Ras-induced senescence is a major defense mechanism suppressing Ras-driven transformation, and loss of functional senescence pathways is necessary for Ras to manifest its full transforming potential (6,52). Although recent studies have confirmed the significance of Ras-induced senescence in vivo, the mechanisms by which Ras can promote a senescent phenotype both in vitro and in vivo remain poorly defined (6,53,54).…”
Section: Discussionmentioning
confidence: 99%
“…Paradoxically, Ras also regulates growth-inhibitory pathways such as apoptosis and senescence (5,50,51). Ras-induced senescence is a major defense mechanism suppressing Ras-driven transformation, and loss of functional senescence pathways is necessary for Ras to manifest its full transforming potential (6,52). Although recent studies have confirmed the significance of Ras-induced senescence in vivo, the mechanisms by which Ras can promote a senescent phenotype both in vitro and in vivo remain poorly defined (6,53,54).…”
Section: Discussionmentioning
confidence: 99%
“…This pathway can trigger both programmed cell death and necrosis. 36 In addition, the Rasa1 gene is a known negative regulator of the Ras pathway via enhancement of activity of the GAP proteins (GTPase-activating proteins). 37 The strain of mice deficient in Rasa1 is characterized by the death of neuronal cells, disorganization of blood vessels, and high embryonic mortality.…”
Section: Discussionmentioning
confidence: 99%
“…The possible carcinogenic mechanism of H-ras is as follows: the mutated H-ras gene results in overexpression of the H-ras protein. The H-ras protein inhibits the activation of a nuclease which triggers apoptosis and leads directly to a significant decrease in cell death (5). It has been found that ras mutation occurs in numerous types of human tumors and that the mutation rate of the ras genes can reach 90% in pancreatic, 40-50% in colon, 40% in lung and 37% in bladder cancer (5).…”
Section: Discussionmentioning
confidence: 99%
“…The H-ras protein inhibits the activation of a nuclease which triggers apoptosis and leads directly to a significant decrease in cell death (5). It has been found that ras mutation occurs in numerous types of human tumors and that the mutation rate of the ras genes can reach 90% in pancreatic, 40-50% in colon, 40% in lung and 37% in bladder cancer (5). The present study showed that H-ras mutation occurred in 49 samples (49/69, 71.01%), of which 19 had a mutation in codon 40, of CTA to CTG, and 30 had a mutation in codon 61, of GGC to AGC.…”
Section: Discussionmentioning
confidence: 99%