title: Fatty acid synthase expression in Barrett's esophagus: implications for carcinogenesis.
abstract: OBJECTIVE
  To investigate the relationship between fatty acid synthase (FASN) expression and the clinicopathological characteristics of Barrett's esophagus and its carcinogenesis.
  
  
  BACKGROUND
  FASN, a key enzyme of the fatty acid biosynthetic pathway, is overexpressed not only in various types of cancer, but also in premalignant conditions. Therefore, FASN overexpression is considered to be indicative of a possible premalignant stage.
  
  
  METHODS
  Patients (N=354) with endoscopically and histologically proven Barrett's esophagus were enrolled. Mucin phenotyping of Barrett's esophagus, expression of FASN and COX-2, cellular proliferation, and apoptosis were evaluated immunohistochemically in biopsy samples, and factors influencing FASN expression were determined by multivariate logistic regression analysis. To evaluate if gastric reflux induces FASN expression, esophageal adenocarcinoma cells were treated with bile acid and low pH, and the effect of a FASN inhibitor on cell proliferation was assessed.
  
  
  RESULTS
  Expression of FASN protein was observed in 52.2% of patients with Barrett's esophagus by immunohistochemistry; this expression pattern was retained in esophageal adenocarcinoma. Intestinal mucin phenotype, COX-2, increased stromal angiogenesis, and elevated proliferating cell nuclear antigen index were confirmed to be positive independent factors for FASN expression. In the esophageal adenocarcinoma cell line SEG-1, FASN mRNA was induced by bile acid with low pH. Cell proliferation was strongly suppressed by the FASN inhibitor C75.
  
  
  CONCLUSIONS
  FASN is strongly expressed in the intestinal mucin phenotype of Barrett's esophagus, in which Barrett's glandular cells display elevated cellular proliferation, angiogenesis, and COX-2 expression. Exposure of the lower esophagus to bile acid with low pH may induce FASN in Barrett's esophagus.
authors.affiliation: Department of Gastroenterology and Hepatology, Shimane University, School of Medicine, Izumo, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ishimura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Amano
authors.forename: Alvaro Adolfo
authors.initials: AA
authors.lastname: Sanchez-Siles
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukuhara
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Goichi
authors.initials: G
authors.lastname: Uno
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tamagawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mishima
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yuki
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D001471:Barrett Esophagus / Q000201:enzymology* / Q000473:pathology; D001647:Bile Acids and Salts / Q000378:metabolism; D001706:Biopsy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2 / Q000032:analysis; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004945:Esophagoscopy; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; D018952:Antigens, CD34; D001647:Bile Acids and Salts; D004791:Enzyme Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D015107:4-Butyrolactone