Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse

被引：1935

作者：

Hingorani, SR

Petricoin, EF

Maitra, A

Rajapakse, V

King, C

Jacobetz, MA

Ross, S

Conrads, TP

Veenstra, TD

Hitt, BA

Kawaguchi, Y

Johann, D

Liotta, LA

Crawford, HC

Putt, ME

Jacks, T

Wright, CVE

Hruban, RH

Lowy, AM

Tuveson, DA ^{[1
]}

机构：

[1] Univ Penn, Abramson Family Canc Res Inst, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Abramson Family Canc Res Inst, Abramson Canc Ctr, Dept Canc Biol, Philadelphia, PA 19104 USA

[3] US FDA, NCI Clin Proteom Program, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA

[4] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Dept Pathol, Baltimore, MD 21287 USA

[5] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Dept Oncol, Baltimore, MD 21287 USA

[6] NCI, Canc Res Ctr, Pathol Lab, FDA,Clin Proteom Program, Bethesda, MD 20892 USA

[7] SAIC Frederick Inc, NCI, Biomed Proteom program, Analyt Chem Lab,Mass Spectrometry Ctr, Ft Detrick, MD 21702 USA

[8] Correlog Syst Inc, Bethesda, MD 20892 USA

[9] Vanderbilt Univ, Dept Cell & Dev Biol, Sch Med, Nashville, TN 37232 USA

[10] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA

[11] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

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

[13] Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[14] Univ Cincinnati, Coll Med, Dept Surg, Div Surg Oncol, Cincinnati, OH 45219 USA

来源：

CANCER CELL | 2003年 / 4卷 / 06期

关键词：

D O I：

10.1016/S1535-6108(03)00309-X

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To evaluate the role of oncogenic RAS mutations in pancreatic tumorigenesis, we directed endogenous expression of KRAS(G12D) to progenitor cells of the mouse pancreas. We find that physiological levels of Kras(G12D) induce ductal lesions that recapitulate the full spectrum of human pancreatic intraepithelial neoplasias (PanINs), putative precursors to invasive pancreatic cancer. The PanINs are highly proliferative, show evidence of histological progression, and activate signaling pathways normally quiescent in ductal epithelium, suggesting potential therapeutic and chemopreventive targets for the cognate human condition. At low frequency, these lesions also progress spontaneously to invasive and metastatic adenocarcinomas, establishing PanINs as definitive precursors to the invasive disease. Finally, mice with PanINs have an identifiable serum proteomic signature, suggesting a means of detecting the preinvasive state in patients.

引用

页码：437 / 450

页数：14

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