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

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Abstract
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.