Document Detail


Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia.
MedLine Citation:
PMID:  19147554     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
E Scott Seeley; Catherine Carrière; Tobias Goetze; Daniel S Longnecker; Murray Korc
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cancer research     Volume:  69     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-16     Completed Date:  2009-02-20     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  422-30     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
CA-101306/CA/NCI NIH HHS; CA-102687/CA/NCI NIH HHS; CA-127095/CA/NCI NIH HHS; P30 CA023108/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:
EC 3.6.5.2/Kras2 protein, mouse; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras)
Comments/Corrections

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