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Cell, Tumor, and Stem Cell Biology

Pancreatic Cancer and Precursor Pancreatic Intraepithelial Neoplasia Lesions Are Devoid of Primary Cilia

E. Scott Seeley, Catherine Carrière, Tobias Goetze, Daniel S. Longnecker and Murray Korc
E. Scott Seeley
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Catherine Carrière
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Tobias Goetze
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Daniel S. Longnecker
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Murray Korc
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DOI: 10.1158/0008-5472.CAN-08-1290 Published January 2009
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Abstract

Primary cilia have been proposed to participate in the modulation of growth factor signaling pathways. In this study, we determined that ciliogenesis is suppressed in both pancreatic cancer cells and pancreatic intraepithelial neoplasia (PanIN) lesions in human pancreatic ductal adenocarcinoma (PDAC). Primary cilia were absent in these cells even when not actively proliferating. Cilia were also absent from mouse PanIN cells in three different mouse models of PDAC driven by an endogenous oncogenic Kras allele. Inhibition of Kras effector pathways restored ciliogenesis in a mouse pancreatic cancer cell line, raising the possibility that ciliogenesis may be actively repressed by oncogenic Kras. By contrast, normal duct, islet, and centroacinar cells retained primary cilia in both human and mouse pancreata. Thus, arrested ciliogenesis is a cardinal feature of PDAC and its precursor PanIN lesions, does not require ongoing proliferation, and could potentially be targeted pharmacologically. [Cancer Res 2009;69(2):422–30]

  • Cilia
  • Kras
  • Pancreatic cancer

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received April 19, 2008.
  • Revision received September 30, 2008.
  • Accepted October 28, 2008.
  • ©2009 American Association for Cancer Research.
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Cancer Research: 69 (2)
January 2009
Volume 69, Issue 2
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  • 2008 SABCS Abstracts: Supplement to Vol. 69, Issue 2

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Pancreatic Cancer and Precursor Pancreatic Intraepithelial Neoplasia Lesions Are Devoid of Primary Cilia
E. Scott Seeley, Catherine Carrière, Tobias Goetze, Daniel S. Longnecker and Murray Korc
Cancer Res January 15 2009 (69) (2) 422-430; DOI: 10.1158/0008-5472.CAN-08-1290

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Pancreatic Cancer and Precursor Pancreatic Intraepithelial Neoplasia Lesions Are Devoid of Primary Cilia
E. Scott Seeley, Catherine Carrière, Tobias Goetze, Daniel S. Longnecker and Murray Korc
Cancer Res January 15 2009 (69) (2) 422-430; DOI: 10.1158/0008-5472.CAN-08-1290
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