ArticleThe Biochemical journal2007
Regulation of the human mucin MUC4 by taurodeoxycholic and taurochenodeoxycholic bile acids in oesophageal cancer cells is mediated by hepatocyte nuclear factor 1alpha.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 61 citations in OpenAlex.
- The Role of Mucin Expression in the Diagnosis of Oesophago-Gastric Cancer: A Systematic Literature Review.Cancers · 2023Review
- Plasma Bile Acid Profiling and Modulation of Secreted Mucin 5AC in Cholangiocarcinoma.International journal of molecular sciences · 2023Article
- P63 Deficiency and CDX2 Overexpression Lead to Barrett's-Like Metaplasia in Mouse Esophageal Epithelium.Digestive diseases and sciences · 2021Article
- The EGF Domains of MUC4 Oncomucin Mediate HER2 Binding Affinity and Promote Pancreatic Cancer Cell Tumorigenesis.Cancers · 2021Article
- Identification of a primitive intestinal transcription factor network shared between esophageal adenocarcinoma and its precancerous precursor state.Genome research · 2019Article
- Current and future roles of mucins in cholangiocarcinoma-recent evidences for a possible interplay with bile acids.Annals of translational medicine · 2018Review
- Article
- Galectin-3 is a non-classic RNA binding protein that stabilizes the mucin MUC4 mRNA in the cytoplasm of cancer cells.Scientific reports · 2017Article
- Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer.Molecular oncology · 2016Article
- Article
- miR-219-1-3p is a negative regulator of the mucin MUC4 expression and is a tumor suppressor in pancreatic cancer.Oncogene · 2015Article
- Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa.International journal of experimental pathology · 2014Article
- Article
- Transcriptional regulation of human MUC4 gene: identification of a novel inhibitory element and its nuclear binding protein.Molecular biology reports · 2013Article
- The MUC4 mucin mediates gemcitabine resistance of human pancreatic cancer cells via the Concentrative Nucleoside Transporter family.Oncogene · 2013Article
- Article
- Molecular mechanisms of Barrett's esophagus.Digestive diseases and sciences · 2011Review
- Transmembrane mucins as novel therapeutic targets.Expert review of endocrinology & metabolism · 2011Article
- Transcriptional regulation of human mucin gene MUC4 in pancreatic cancer cells.Molecular biology reports · 2010Article
- Inflammation modulates the expression of the intestinal mucins MUC2 and MUC4 in gastric tumors.Oncogene · 2010Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MUC4 (mucin 4) is a membrane-bound mucin overexpressed in the early steps of oesophageal carcinogenesis and implicated in tumour progression. We previously showed that bile acids, main components of gastro-oesophageal reflux and tumour promoters, up-regulate MUC4 expression [Mariette, Perrais, Leteurtre, Jonckheere, Hemon, Pigny, Batra, Aubert, Triboulet and Van Seuningen (2004) Biochem. J. 377, 701-708]. HNF (hepatocyte nuclear factor) 1alpha and HNF4alpha transcription factors are known to mediate bile acid effects, and we previously identified cis-elements for these factors in MUC4 distal promoter. Our aim was to demonstrate that these two transcription factors were directly involved in MUC4 activation by bile acids. MUC4, HNF1alpha and HNF4alpha expressions were evaluated by immunohistochemistry in human oesophageal tissues. Our results indicate that MUC4, HNF1alpha and HNF4alpha were co-expressed in oesophageal metaplastic and adenocarcinomatous tissues. Studies at the mRNA, promoter and protein levels indicated that HNF1alpha regulates endogenous MUC4 expression by binding to two cognate cis-elements respectively located at -3332/-3327 and -3040/-3028 in the distal promoter. We also showed by siRNA (small interfering RNA) approach, co-transfection and site-directed mutagenesis that HNF1alpha mediates taurodeoxycholic and taurochenodeoxycholic bile acid activation of endogenous MUC4 expression and transcription in a dose-dependent manner. In conclusion, these results describe a new mechanism of regulation of MUC4 expression by bile acids, in which HNF1alpha is a key mediator. These results bring new insights into MUC4 up-regulation in oesophageal carcinoma associated with bile reflux.
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