The effect of LKB1 on the PI3K/Akt pathway activation in association with PTEN and PIK3CA in HNC.

Abstract

PI3K/Akt signalling pathway is frequently activated in several types of cancer. However, activator molecules have not been analysed systematically in HNSCC. The aim of this study was to investigate upstream activators and inhibitors of this pathway. Prospective study. University hospital. 108 patients with HNC who were operated at the Istanbul University, Cerrahpasa Medical Faculty, Department of Otorhinolaryngology. Mutations in the coding exons and the flanking intronic sequences of the PIK3CA, PIK3R1 and AKT1 genes were analysed by direct sequencing. Expression levels in the tumours and non-cancerous tissue samples were analysed by quantitative RT-PCR, and Western blotting was performed to determine the phosphorylation levels of the Akt1 protein. Two synonymous alterations in exon 20 of the PIK3CA gene, a 6-bp duplication in the coding region of the PIK3R1 and two different alterations in the non-coding regions of the AKT1 and PIK3R1 genes were observed. Significant downregulation of LKB1 and PTEN mRNA expression levels were detected in tumour tissues compared to non-cancerous tissues. However, we did not observe any difference between the PIK3CA and AKT1 mRNA expression levels in the tumours and non-cancerous tissue samples. Akt1 phosphorylation was increased in 53.57% of the patients. Our results indicate that the PI3K pathway has an important function in HNSCC progression with the contribution of more than one gene of this pathway. Our data suggest that in a high number of HNSCC tumours, PI3K/Akt signalling is activated by different molecules or by the combination of these molecules.