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The effect of LKB 1 on the PI 3K/Akt pathway activation in association with PTEN and PIK 3 CA in HNC
Author(s) -
Ekizoglu S.,
Dogan S.,
Ulker D.,
Seven D.,
Gozen E.D.,
Karaman E.,
Buyru N.
Publication year - 2015
Publication title -
clinical otolaryngology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.914
H-Index - 68
eISSN - 1749-4486
pISSN - 1749-4478
DOI - 10.1111/coa.12427
Subject(s) - pten , protein kinase b , akt1 , exon , pi3k/akt/mtor pathway , gene , cancer research , activator (genetics) , phosphorylation , medicine , coding region , messenger rna , signal transduction , microbiology and biotechnology , biology , genetics
Objective PI 3K/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. Design Prospective study. Setting University hospital. Participants 108 patients with HNC who were operated at the Istanbul University, Cerrahpasa Medical Faculty, Department of Otorhinolaryngology. Methods Mutations in the coding exons and the flanking intronic sequences of the PIK 3 CA , PIK 3R1 and AKT 1 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. Results Two synonymous alterations in exon 20 of the PIK 3 CA gene, a 6‐bp duplication in the coding region of the PIK 3R1 and two different alterations in the non‐coding regions of the AKT 1 and PIK 3R1 genes were observed. Significant downregulation of LKB 1 and PTEN mRNA expression levels were detected in tumour tissues compared to non‐cancerous tissues. However, we did not observe any difference between the PIK 3 CA and AKT 1 mRNA expression levels in the tumours and non‐cancerous tissue samples. Akt1 phosphorylation was increased in 53.57% of the patients. Conclusions Our results indicate that the PI 3K 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, PI 3K/Akt signalling is activated by different molecules or by the combination of these molecules.