2004
DOI: 10.1016/s1535-6108(04)00085-6
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Abstract: Activating mutations in the ras oncogene are not considered sufficient to induce abnormal cellular proliferation in the absence of cooperating oncogenes. We demonstrate that the conditional expression of an endogenous K-ras(G12D) allele in murine embryonic fibroblasts causes enhanced proliferation and partial transformation in the absence of further genetic abnormalities. Interestingly, K-ras(G12D)-expressing fibroblasts demonstrate attenuation and altered regulation of canonical Ras effector signaling pathway… Show more

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Cited by 696 publications
(697 citation statements)
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“…Additionally, withdrawal of oncogenic K-Ras expression resulted in loss of tumours indicating a reliance on K-Ras signalling for maintenance of the tumours as seen earlier with H-Ras induced melanomas [27]. Finally, expression of oncogenic Ras during embryogenesis was embryonic lethal [19,26]; when combined with the knockout mouse data this indicates that a precise pattern of regulated Ras isoform signalling is required for normal development.…”
Section: Introductionmentioning
confidence: 63%
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“…Additionally, withdrawal of oncogenic K-Ras expression resulted in loss of tumours indicating a reliance on K-Ras signalling for maintenance of the tumours as seen earlier with H-Ras induced melanomas [27]. Finally, expression of oncogenic Ras during embryogenesis was embryonic lethal [19,26]; when combined with the knockout mouse data this indicates that a precise pattern of regulated Ras isoform signalling is required for normal development.…”
Section: Introductionmentioning
confidence: 63%
“…Deletion of components of the tumour suppressor pathway such as ARF are needed to generate the hyperproliferative state and induce carcinogenesis [25]. However, in contrast to these in vitro studies where supraphysiological levels of Ras are expressed, mouse embryonic fibroblasts (MEFs) derived from mice engineered to express endogenous levels of oncogenic K-Ras are immortalised and do not become senescent [19,26].…”
Section: Introductionmentioning
confidence: 99%
“…Initial reports demonstrated that this allele promoted hyperplasia and tumor development in a subset of tissues. Moreover, this allele did not induce the cellular senescence of mouse embryonic fibroblasts (MEFs), but rather resulted in their immortalization, supporting the possibility that at least in this cell type, senescence might be an artifact of Ras overexpression (Tuveson et al, 2004).…”
Section: History Of Oncogene-induced Senescencementioning
confidence: 97%
“…Opponents of the concept speculated that it might be an in vitro phenomenon caused by supraphysiological levels of activated Ras. This hypothesis was fueled by the development and characterization of mouse models that were designed to express a single activated K-ras allele driven by its endogenous promoter (Guerra et al, 2003;Tuveson et al, 2004). Initial reports demonstrated that this allele promoted hyperplasia and tumor development in a subset of tissues.…”
Section: History Of Oncogene-induced Senescencementioning
confidence: 99%
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