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Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we determined the effect of PDAC-relevant gene mutations in distinct cell types of the adult pancreas. We show that a subpopulation of Pdx1-expressing cells is susceptible to oncogenic K-Ras-induced transformation without tissue injury, whereas insulin-expressing endocrine cells are completely refractory to transformation under these conditions. However, chronic pancreatic injury can alter their endocrine fate and allow them to serve as the cell of origin for exocrine neoplasia. These results suggest that one mechanism by which inflammation and/or tissue damage can promote neoplasia is by altering the fate of differentiated cells that are normally refractory to oncogenic stimulation.

SUBMITTER: Gidekel Friedlander SY

PROVIDER: S-EPMC3048064 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras.

Gidekel Friedlander Sharon Y SY Chu Gerald C GC Snyder Eric L EL Girnius Nomeda N Dibelius Gregory G Crowley Denise D Vasile Eliza E DePinho Ronald A RA Jacks Tyler T

Cancer cell 20091101 5

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we determined the effect of PDAC-relevant gene mutations in distinct cell types of the adult pancreas. We show that a subpopulation of Pdx1-expressing cells is susceptible to oncogenic K-Ras-induced transformation without tissue injury, whereas insulin-expressing endocrine cells are completely refractory to transformation under these conditions. However, chr ...[more]

PMID: 19878870

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