Cyclin D 1‐induced proliferation is independent of beta‐catenin in H ead and N eck C ancer

Objective Head and neck squamous cell carcinoma ( HNSCC ) progression and metastasis have previously been associated with the activation of phosphatidylinositol 3‐kinase‐protein kinase B ( P I3 K ‐ A kt) and Wnt signalling pathways, which lead to the activation of pro‐proliferative genes, such as cyclin D 1. The current study aims to investigate whether there is a crosstalk between these pathways in HNSCC and which pathway is more likely to regulate cyclin D 1. Material and Methods Two HNSCC and a control keratinocyte cell lines were treated with EGF and wortmannin to respectively activate and block the P I3 K ‐ A kt and W nt pathways. Partial and total levels of cyclin D 1, beta‐catenin and Akt were evaluated by W estern blotting and immunofluorescence. Twenty‐four paraffin‐embedded samples of human HNSCC , as well as normal oral mucosa biopsies, were also immunohistochemically evaluated for beta‐catenin and cyclin D 1 expression. Results Following both treatments, change in cyclin D 1 protein was correlated with A kt levels only. Cytoplasmic staining for beta‐catenin and loss of its membranous expression in the HNSCC invasive areas were found in 92% of the HNSCC biopsies. Conclusion Taken together, we show that the change in cyclin D 1 levels is more likely to be due to the EGFR ‐ A kt pathway activation than due to beta‐catenin nuclear translocation.