β-catenin transcriptional activity is inhibited downstream of nuclear localisation and is not influenced by IGF signalling in oesophageal cancer cells

Aberrant expression/localisation of β-catenin has been implicated in the progression of oesophageal cancer. As a member of the Wnt-signalling pathway, activated β-catenin translocates into the nucleus and drives gene transcription. Insulin-like growth factors (IGFs) have been implicated in modulation of β-catenin localisation and transcriptional activity. We have demonstrated that β-catenin is abundantly expressed by oesophageal cancer cells, and is both cytoplasmic and nuclear in location, β-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 β-catenin/T-cell factor- (TCF) mediated transcription. Activation of Wnt signalling by lithium induced β-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 β-catenin did exhibit β-catenin/TCF-mediated transcriptional activity. This study shows that β-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.