Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice - PubMed

Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice

Sunil R Hingorani et al. Cancer Cell. 2005 May.

Free article

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 observed in mice. No mutations were discovered in other cardinal tumor suppressor gene pathways, which, together with previous results, suggests that there are distinct genetic pathways to PDA with different biological behaviors. These findings have clear implications for understanding mechanisms of disease pathogenesis, and for the development of detection and targeted treatment strategies.

Comment in

• Chromosomal instability in mouse metastatic pancreatic cancer--it's Kras and Tp53 after all.

  Siveke JT, Schmid RM. Siveke JT, et al. Cancer Cell. 2005 May;7(5):405-7. doi: 10.1016/j.ccr.2005.04.025. Cancer Cell. 2005. PMID: 15894260

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