title: In vitro model for gastroduodenal reflux-induced nuclear factor-kappaB activation and its role in hypopharyngeal carcinogenesis.
abstract: The purpose of this study was to investigate whether gastroduodenal reflux can play a role in the pathogenesis of hypopharyngeal cancer; therefore, we assessed its effect on the nuclear factor-kappa B (NF-κB) pathway, as similarly noted in the esophagus.
  
  
  
  We exposed human cells derived from the hypopharyngeal epithelium to bile acids or deoxycholic acid. We centered our study on the transcriptional activation of NF-κB pathway, previously linked to head and neck squamous cell carcinoma (HNSCC).
  
  
  
  We show that acidic-bile salts induce: (1) NF-κB activation with high cytoplasmic Bcl-2 expression; (2) significant increase in expression v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA(p65)), v-rel avian reticuloendotheliosis viral oncogene homolog (c-REL) signal transducer and activator of transcription 3 (STAT3), isoform of transformation related protein p63 (ΔNp63), B-cell lymphoma 2 (Bcl-2), tumor necrosis factor alpha (TNF-α), epidermal growth factor receptor (EGFR), and wingless type MMTV integration site family member 5A (WNT5A) and a decrease in tumor protein p53 (Tp53); and (3) phenotypic changes that are similar to the phenotype of the untreated hypopharyngeal cancer cell line, University of Michigan squamous cell carcinoma (UMSCC)-11B. These changes are not seen when cells were exposed to neutral control or acid alone.
  
  
  
  Our findings in vitro are consistent with the hypothesis that gastroduodenal reflux plays a role in hypopharyngeal carcinogenesis and its effect is mediated through activation of NF-κB pathway. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1381-E1391, 2016.
authors.affiliation: Department of Surgery, Section of Otolaryngology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Clarence T
authors.initials: CT
authors.lastname: Sasaki
authors.affiliation: Department of Surgery, Section of Otolaryngology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Natalia
authors.initials: N
authors.lastname: Issaeva
authors.affiliation: Department of Surgery, Section of Otolaryngology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Dimitra P
authors.initials: DP
authors.lastname: Vageli
mesh_terms: D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D004383:Duodenogastric Reflux / Q000503:physiopathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000473:pathology*; D007013:Hypopharynx / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B
keywords: bile acids; gastroduodenal reflux; hypopharyngeal cancer; in vitro; nuclear factor-kappa B (NF-κB)