title: Beta-catenin signaling induces CYP1A1 expression by disrupting adherens junctions in Caco-2 human colon carcinoma cells.
abstract: BACKGROUND
  The aryl hydrocarbon (Ah) receptor is one of the best known ligand-activated transcription factors. The present study has focused on the wound-healing process on Ah receptor function.
  
  
  METHODS
  Depletion of calcium from culture medium of Caco-2 human colon carcinoma cells by transfer to Minimal Essential Medium (Spinner Modification; S-MEM) destroyed adherens junctions and the cells were used as the model of wound-healing process.
  
  
  RESULTS
  Calcium depletion induced both nuclear translocation of the Ah receptor, and increased expression of CYP1A1 and Slug mRNAs in Caco-2 cells. However, expression of Slug mRNA was not significantly induced by treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Knockdown of the Ah receptor and treatment with Ah receptor antagonists decreased level of CYP1A1 mRNA. The fragment of E-cadherin released by gamma-secretase was not involved in induction of CYP1A1 mRNA following S-MEM treatment. Knockdown of beta-catenin increased levels of Ah receptor mRNA, which may be attributable to direct or indirect involvement of beta-catenin in suppression of the Ah receptor gene.
  
  
  CONCLUSIONS
  Our results suggest that mRNA induction of some genes by destruction of adherens junctions depends on the Ah receptor. beta-Catenin, one of the components of the adherens junction, was released from the E-cadherin complex, which resulted in its increased interaction with the Ah receptor, and was translocated into the nucleus, and consequently the target genes would be transcribed.
  
  
  CONCLUSIONS
  Our observations suggest that some aspects of the molecular mechanism of wound healing involve the Ah receptor.
authors.affiliation: Science of Biosources, United Graduate School of Agricultural Science, Iwate University, Morioka 020-8551, Japan.
authors.forename: Shuya
authors.initials: S
authors.lastname: Kasai
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishigaki
authors.forename: Ryo
authors.initials: R
authors.lastname: Takumi
authors.forename: Toru
authors.initials: T
authors.lastname: Kamimura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kikuchi
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000172:deficiency; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003470:Culture Media; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D003470:Culture Media; D010446:Peptide Fragments; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; D053829:Amyloid Precursor Protein Secretases; D002118:Calcium