Send to

Choose Destination
Oncotarget. 2016 Feb 2;7(5):5892-908. doi: 10.18632/oncotarget.6824.

Gastro-duodenal fluid induced nuclear factor-κappaB activation and early pre-malignant alterations in murine hypopharyngeal mucosa.

Author information

Department of Surgery,Yale Larynx Laboratory Section of Otolaryngology, Yale School of Medicine, New Haven, CT, USA.
Pathology and of Surgery (Otolaryngology), Yale School of Medicine, New Haven, CT, USA.


We recently described the role of gastro-duodenal fluids (GDFs) in generating changes consistent with hypopharyngeal neoplasia through activation of NF-κB pathway, using an in vitro model of human hypopharyngeal normal keratinocytes. Here, we further provide evidence that gastro-duodenal reflux is a risk factor for early pre-malignant alterations in hypopharyngeal mucosa (HM) related to an activated NF-κB oncogenic pathway, using both an in vitro and a novel in vivo model of C57Bl/6J mice. Histological, immunohistochemical and automated quantitative analysis documents significant NF-κB activation and early pre-malignant alterations in HM topically exposed to GDFs, compared to acid alone and other controls. Early pre-malignant histologic lesions exhibited increased Ki67, CK14 and ΔNp63, cell proliferation markers, changes of cell adhesion molecules, E-Cadherin and β-catenin, and STAT3 activation. The in vivo effect of NF-κB activation is positively correlated with p-STAT3, Ki67, CK14 or β-catenin expression, while GDFs induce significant transcriptional activation of RELA(p65), bcl-2, TNF-α, STAT3, EGFR and wnt5A, in vivo. Our in vivo model demonstrates selectively activated NF-κB in response to topically administrated GDFs, leading to early pre-malignant events in HM.


NF-κB; bile acids; gastroduodenal reflux; hypopharyngeal cancer; in vivo

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center