| Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia. | |
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MedLine Citation:
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PMID: 19147554 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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E Scott Seeley; Catherine Carrière; Tobias Goetze; Daniel S Longnecker; Murray Korc |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Cancer research Volume: 69 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-16 Completed Date: 2009-02-20 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 422-30 Citation Subset: IM |
Affiliation:
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Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03756, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carcinoma, Pancreatic Ductal / genetics, pathology*, ultrastructure Cell Growth Processes / physiology Cell Line, Tumor Centrosome / pathology Cilia / pathology Epithelial Cells / pathology Genes, ras Humans Mice Mice, Transgenic Pancreatic Neoplasms / genetics, pathology*, ultrastructure Precancerous Conditions / genetics, pathology*, ultrastructure Proto-Oncogene Proteins p21(ras) / antagonists & inhibitors, genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA-101306/CA/NCI NIH HHS; CA-102687/CA/NCI NIH HHS; CA-127095/CA/NCI NIH HHS; R01 CA101306/CA/NCI NIH HHS; R01 CA101306-05/CA/NCI NIH HHS; R01 CA102687/CA/NCI NIH HHS; R01 CA102687-05/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 3.6.5.2/Kras2 protein, mouse; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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