Context-Dependent Transformation of Adult Pancreatic Cells by Oncogenic K-Ras

被引：268

作者：

Friedlander, Sharon Y. Gidekel ^{[1
]}

Chu, Gerald C. ^{[4
,5
,6
]}

Snyder, Eric L. ^{[1
,5
]}

Girnius, Nomeda ^{[1
]}

Dibelius, Gregory ^{[1
]}

Crowley, Denise ^{[1
,3
]}

Vasile, Eliza ^{[1
]}

DePinho, Ronald A. ^{[4
,6
,7
]}

Jacks, Tyler ^{[1
,2
,3
]}

机构：

[1] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

[3] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[4] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[5] Brigham & Womans Hosp, Dept Pathol, Boston, MA 02115 USA

[6] Belfer Fdn Inst Innovat Canc Sci, Ctr Appl Canc Sci, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA

来源：

CANCER CELL | 2009年 / 16卷 / 05期

基金：

美国国家卫生研究院;

关键词：

MALIGNANT-TRANSFORMATION; MOUSE MODEL; BETA-CELLS; EXPRESSION; CANCER; LET-7; PROGENITORS; NEOPLASIA; HEDGEHOG; LINEAGE;

D O I：

10.1016/j.ccr.2009.09.027

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：379 / 389

页数：11

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