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

Sunil R. Hingorani, Lifu Wang, Asha S. Multani, Chelsea Combs, Therese B. Deramaudt, Ralph H Hruban, Anil K. Rustgi, Sandy Chang, David A. Tuveson

Research output: Contribution to journalArticle

Abstract

To define the genetic requirements for pancreatic ductal adenocarcinoma (PDA), we have targeted concomitant endogenous expression of Trp53 R172H and KrasG12D 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.

Original languageEnglish (US)
Pages (from-to)469-483
Number of pages15
JournalCancer Cell
Volume7
Issue number5
DOIs
StatePublished - May 2005

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Chromosomal Instability
Adenocarcinoma
Carcinoma
Genomic Instability
Telomere
Tumor Suppressor Genes
Pancreas
Neoplasm Metastasis
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. / Hingorani, Sunil R.; Wang, Lifu; Multani, Asha S.; Combs, Chelsea; Deramaudt, Therese B.; Hruban, Ralph H; Rustgi, Anil K.; Chang, Sandy; Tuveson, David A.

In: Cancer Cell, Vol. 7, No. 5, 05.2005, p. 469-483.

Research output: Contribution to journalArticle

Hingorani, SR, Wang, L, Multani, AS, Combs, C, Deramaudt, TB, Hruban, RH, Rustgi, AK, Chang, S & Tuveson, DA 2005, 'Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice', Cancer Cell, vol. 7, no. 5, pp. 469-483. https://doi.org/10.1016/j.ccr.2005.04.023
Hingorani, Sunil R. ; Wang, Lifu ; Multani, Asha S. ; Combs, Chelsea ; Deramaudt, Therese B. ; Hruban, Ralph H ; Rustgi, Anil K. ; Chang, Sandy ; Tuveson, David A. / Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. In: Cancer Cell. 2005 ; Vol. 7, No. 5. pp. 469-483.
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AU - Deramaudt, Therese B.

AU - Hruban, Ralph H

AU - Rustgi, Anil K.

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