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

Sunil R. Hingorani, Emanuel F. Petricoin, Anirban Maitra, Vinodh Rajapakse, Catrina King, Michael A. Jacobetz, Sally Ross, Thomas P. Conrads, Timothy D. Veenstra, Ben A. Hitt, Yoshiya Kawaguchi, Don Johann, Lance A. Liotta, Howard C. Crawford, Mary E. Putt, Tyler Jacks, Christopher V E Wright, Ralph H. Hruban, Andrew M. Lowy, David A. Tuveson

Research output: Contribution to journalArticle

1366 Citations (Scopus)

Abstract

To evaluate the role of oncogenic RAS mutations in pancreatic tumorigenesis, we directed endogenous expression of KRASG12D to progenitor cells of the mouse pancreas. We find that physiological levels of KrasG12D 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.

Original languageEnglish (US)
Pages (from-to)437-450
Number of pages14
JournalCancer Cell
Volume4
Issue number6
DOIs
StatePublished - Dec 2003
Externally publishedYes

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Pancreatic Neoplasms
Neoplasms
Proteomics
Pancreas
Carcinogenesis
Adenocarcinoma
Stem Cells
Epithelium
Mutation
Serum
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., ... Tuveson, D. A. (2003). Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell, 4(6), 437-450. https://doi.org/10.1016/S1535-6108(03)00309-X

Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. / Hingorani, Sunil R.; Petricoin, Emanuel F.; Maitra, Anirban; Rajapakse, Vinodh; King, Catrina; Jacobetz, Michael A.; Ross, Sally; Conrads, Thomas P.; Veenstra, Timothy D.; Hitt, Ben A.; Kawaguchi, Yoshiya; Johann, Don; Liotta, Lance A.; Crawford, Howard C.; Putt, Mary E.; Jacks, Tyler; Wright, Christopher V E; Hruban, Ralph H.; Lowy, Andrew M.; Tuveson, David A.

In: Cancer Cell, Vol. 4, No. 6, 12.2003, p. 437-450.

Research output: Contribution to journalArticle

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 2003, 'Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse', Cancer Cell, vol. 4, no. 6, pp. 437-450. https://doi.org/10.1016/S1535-6108(03)00309-X
Hingorani SR, Petricoin EF, Maitra A, Rajapakse V, King C, Jacobetz MA et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 2003 Dec;4(6):437-450. https://doi.org/10.1016/S1535-6108(03)00309-X
Hingorani, Sunil R. ; Petricoin, Emanuel F. ; Maitra, Anirban ; Rajapakse, Vinodh ; King, Catrina ; Jacobetz, Michael A. ; Ross, Sally ; Conrads, Thomas P. ; Veenstra, Timothy D. ; Hitt, Ben A. ; Kawaguchi, Yoshiya ; Johann, Don ; Liotta, Lance A. ; Crawford, Howard C. ; Putt, Mary E. ; Jacks, Tyler ; Wright, Christopher V E ; Hruban, Ralph H. ; Lowy, Andrew M. ; Tuveson, David A. / Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. In: Cancer Cell. 2003 ; Vol. 4, No. 6. pp. 437-450.
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