Oncogenic KRas suppresses inflammation-associated senescence of pancreatic ductal cells.

Abstract:

:Mutational activation of KRas is the first and most frequently detected genetic lesion in pancreatic ductal adenocarcinoma (PDAC). However, the precise role of oncogenic KRas in the pathogenesis of PDAC is not fully understood. Here, we report that the endogenous expression of oncogenic KRas suppresses premature senescence in primary pancreatic duct epithelial cells (PDEC). Oncogenic KRas-mediated senescence bypass is conferred by the upregulation of the basic helix-loop-helix transcription factor Twist that in turn abrogates p16(INK4A) induction. Moreover, the KRas-Twist-p16(INK4A) senescence bypass pathway is employed in vivo to prevent inflammation-associated senescence of pancreatic ductal epithelium. Our findings indicate that oncogenic KRas could contribute to PDAC initiation by protecting cells from entering a state of permanent growth arrest.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Lee KE,Bar-Sagi D

doi

10.1016/j.ccr.2010.10.020

subject

Has Abstract

pub_date

2010-11-16 00:00:00

pages

448-58

issue

5

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(10)00422-8

journal_volume

18

pub_type

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