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Farnesoid X Receptor Expression Is Decreased in Colonic Mucosa of Patients with Primary Sclerosing Cholangitis and Colitis-associated Neoplasia.
MedLine Citation:
PMID:  23348121     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND:: The expression and distribution of farnesoid X receptor (FXR) in colitis and colitis-associated neoplasia (CAN) is unknown. We investigated FXR expression in neoplastic and nonneoplastic tissue from ulcerative colitis (UC) patients, with or without primary sclerosing cholangitis (PSC), as well as the role of DNA methylation in FXR expression in colorectal cancer (CRC) cell lines. METHODS:: Samples from the right (RC) and left (LC) colon of patients with UC, with and without PSC, and with or without CAN, were stained by immunohistochemistry and scored semiquantitatively for nuclear FXR expression. FXR expression was analyzed by western blot and polymerase chain reaction (PCR) in nine different CRC cell lines before and after demethylation with 5-azacytidine. RESULTS:: In nondysplastic samples, FXR expression demonstrated a diminishing expression from proximal to distal colon (strong FXR expression: 39% RC samples vs. 14% LC samples; P = 0.007). With moderate-to-severe inflammation, FXR expression was almost always absent or weak in both UC and PSC-UC, regardless of location. With quiescent/mild inflammation, 56% of UC samples in the RC retained strong FXR expression versus 24% of PSC-UC samples (P= 0.017). FXR was absent in 72% of the neoplastic samples, with an inverse association with the grade of dysplasia. FXR expression was absent in all CRC cell lines, in some cases due to DNA methylation. CONCLUSIONS:: FXR expression is inversely correlated with neoplastic progression and severity of inflammation in UC. Patients with PSC-UC have diminished FXR expression in the proximal colon compared to UC patients. This finding could contribute to the higher risk of proximal neoplasia in PSC patients.
Authors:
Joa Na Torres; Xiuliang Bao; Alina C Iuga; Anli Chen; Noam Harpaz; Thomas Ullman; Benjamin L Cohen; Guillaume Pineton de Chambrun; Stefania Asciutti; Joseph A Odin; David B Sachar; H Rex Gaskins; Kenneth Setchell; Jean-Frédéric Colombel; Steven H Itzkowitz
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-23
Journal Detail:
Title:  Inflammatory bowel diseases     Volume:  -     ISSN:  1536-4844     ISO Abbreviation:  Inflamm. Bowel Dis.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508162     Medline TA:  Inflamm Bowel Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
*Dr. Henry D. Janowitz Division of Gastroenterology, Mount Sinai School of Medicine, New York, New York, USA †Gastroenterology Service, Surgery Department, Hospital Beatriz Ângelo, Loures, Portugal ‡Division of Gastrointestinal Pathology, Mount Sinai School of Medicine, New York, New York, USA §Inserm Unit 995, Université Lille Nord de France, Lille, France ‖Department of Medicine, School of Medicine, UCSD, San Diego, California, USA ¶Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York, USA **Division of Liver Disease and Recanati/Miller Transplantation Institute, The Mount Sinai Hospita Mount Sinai School of Medicine, New York, New York, USA ††Departments of Animal Sciences and Pathobiology, Division of Nutritional Sciences, Institute for Genomic Biology. University of Illinois at Urbana-Champaign, Urbana, Illinois, USA ‡‡Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio USA §§Department of Hepatogastroenterology, Hôpital Claude Huriez and Centre d'Investigation Clinique, Centre Hospitalier Universitaire de Lille, Université Lille Nord de France, Lille, France.
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