title: Beta-catenin transcriptional activity is inhibited downstream of nuclear localisation and is not influenced by IGF signalling in oesophageal cancer cells.
abstract: Aberrant expression/localisation of beta-catenin has been implicated in the progression of oesophageal cancer. As a member of the Wnt-signalling pathway, activated beta-catenin translocates into the nucleus and drives gene transcription. Insulin-like growth factors (IGFs) have been implicated in modulation of beta-catenin localisation and transcriptional activity. We have demonstrated that beta-catenin is abundantly expressed by oesophageal cancer cells, and is both cytoplasmic and nuclear in location. beta-catenin was transcriptionally inactive in 4 of 5 cell lines. All cells expressed the IGF-1 receptor. Addition of exogenous IGFs activated the PI-3 kinase pathway but did not enhance beta-catenin/T-cell factor- (TCF) mediated transcription. Activation of Wnt signalling by lithium induced beta-catenin stabilisation in 2 cell lines but this did not increase transcriptional activity. In contrast 2 cell lines without lithium-enhanced stabilisation or re-distribution of beta-catenin did exhibit beta-catenin/TCF-mediated transcriptional activity. This study shows that beta-catenin accumulation and nuclear localisation is not indicative of transcriptional activity, and therefore is not supportive of a major role in these oesophageal cancer cells. It also questions the value of immunohistochemical studies that examine only expression. Co-operative signalling from other growth factors or adhesive molecules is likely to be required to relieve nuclear inhibition of transcriptional activity, and the nature of this is currently unknown.
authors.affiliation: Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute & Mercy University Hospital, University College Cork, Cork, Ireland.
authors.forename: B
authors.initials: B
authors.lastname: Kiely
authors.affiliation: Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute & Mercy University Hospital, University College Cork, Cork, Ireland.
authors.forename: R T
authors.initials: RT
authors.lastname: O'Donovan
authors.affiliation: Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute & Mercy University Hospital, University College Cork, Cork, Ireland.
authors.forename: S L
authors.initials: SL
authors.lastname: McKenna
authors.affiliation: Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute & Mercy University Hospital, University College Cork, Cork, Ireland.
authors.forename: G C
authors.initials: GC
authors.lastname: O'Sullivan
mesh_terms: D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism*
chemical_list: D008024:Ligands; D012333:RNA, Messenger; D051820:TCF Transcription Factors; D051176:beta Catenin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II