2005
DOI: 10.1016/j.ccr.2005.04.023
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Abstract: To define the genetic requirements for pancreatic ductal adenocarcinoma (PDA), we have targeted concomitant endogenous expression of Trp53(R172H) and Kras(G12D) to the mouse pancreas, revealing the cooperative development of invasive and widely metastatic carcinoma that recapitulates the human disease. The primary carcinomas and metastases demonstrate a high degree of genomic instability manifested by nonreciprocal translocations without obvious telomere erosion-hallmarks of human carcinomas not typically obse… Show more

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Cited by 2,097 publications
(2,302 citation statements)
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References 49 publications
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“…Our findings are consistent with observations of mutant p53 GOF in mouse models where expression of the mouse R172H mutant (equivalent to human R175H) results in tumours showing centrosome amplification and an associated aneuploidy (Murphy et al, 2000;Hingorani et al, 2005;Caulin et al, 2007). However, these previous reports are confounded as they use a K-Ras G12D mutation as an initiating oncogenic event (Hingorani et al, 2005;Caulin et al, 2007). Our data show that mutant p53 alone is sufficient to drive the observed GOF phenotype.…”
Section: Input Igg Pab1620supporting
confidence: 91%
“…Our findings are consistent with observations of mutant p53 GOF in mouse models where expression of the mouse R172H mutant (equivalent to human R175H) results in tumours showing centrosome amplification and an associated aneuploidy (Murphy et al, 2000;Hingorani et al, 2005;Caulin et al, 2007). However, these previous reports are confounded as they use a K-Ras G12D mutation as an initiating oncogenic event (Hingorani et al, 2005;Caulin et al, 2007). Our data show that mutant p53 alone is sufficient to drive the observed GOF phenotype.…”
Section: Input Igg Pab1620supporting
confidence: 91%
“…It is now becoming more generally apparent that many mouse tissues designed to express this single K-ras allele do not exhibit much if any ERK and AKT activation (Kim et al, 2005). In contrast, when these mice are crossed to other tumor-prone strains to generate animals with compound mutations, the resulting tumors do exhibit activation of Ras effectors, implying that this suppression is somehow alleviated in the course of tumor development and/or progression (Dinulescu et al, 2005;Hingorani et al, 2005).…”
Section: Mechanisms Of Oncogene-induced Senescence S Courtois-cox Et Almentioning
confidence: 99%
“…Cooperative mutations in proto-oncogenes and tumor suppressor genes occur in many forms of cancer. 27,28 The model of cooperative mutations causing a reduction in Ikaros activity and an increase in Notch1 activation fits this paradigm in the genesis of T-ALL. 30,44 However, most Notch1 mutations found in TL do not generate signals of sufficient strength to initiate leukemia development and require other leukemogenic factors.…”
Section: Discussionmentioning
confidence: 79%