title: Activation of the canonical WNT signaling pathway promotes ovarian surface epithelial proliferation without inducing β-catenin/Tcf-mediated reporter expression.
abstract: BACKGROUND
  In response to activation of the canonical WNT signaling pathway, β-catenin cooperates with Lef/Tcf (lymphoid enhancer factor/T-cell factor) transcription factors to drive expression of Wnt target genes. The canonical WNT signaling pathway is involved in development, wound repair, and tumorigenesis. Studies examining the involvement of the canonical WNT signaling pathway in the development of ovarian surface epithelium (OSE) and ovarian carcinogenesis, however, have recently begun to emerge. In this study, we investigated the modulation of β-catenin and β-catenin/Tcf-signaling activity within the OSE using responsive transgenic mice and examined the response of primary OSE cells and ovarian cancer cell lines to activation of the canonical WNT signaling pathway.
  
  
  RESULTS
  β-catenin was localized to the lateral membrane of the ovarian epithelium. Stimulation of primary OSE cells in vitro with LiCl or Wnt3a led to GSK-3β inhibition and stabilization of β-catenin but failed to induce β-catenin/Tcf-mediated lacZ expression. Furthermore, E-cadherin expression was downregulated and the proliferative potency of OSE cells increased. Of four ovarian cancers cell lines screened, only the HEY cell line demonstrated induction of luciferase reporter upon canonical WNT stimulation.
  
  
  CONCLUSIONS
  These observations suggest that in ovarian adenocarcinoma, dysregulated WNT signaling may not always be indicative of β-catenin/Tcf-mediated transcriptional activity.
authors.affiliation: Department of Experimental Medicine, McGill University, Montreal, Canada. macalister.usongo@mail.mcgill.ca
authors.forename: Macalister
authors.initials: M
authors.lastname: Usongo
authors.forename: Xinfang
authors.initials: X
authors.lastname: Li
authors.forename: Riaz
authors.initials: R
authors.lastname: Farookhi
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017930:Genes, Reporter / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018692:Antimanic Agents; D051820:TCF Transcription Factors; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride