Abstract 1800: Expression analysis of PI3K pathway genes in head and neck cancer.

Head and neck cancer (HNC) is a heterogenous group of malignant tumors which includes neoplasias of the oral cavity, the pharynx, the larynx and paranasal sinuses. Squamous cell carcinomas comprise more than 95% of all head and neck cancers. The vast majority of HNC is related to exposure to carcinogens, including tobacco, alcohol, betel nut, and sexually transmitted viral pathogens such as human papilloma viruses (HPV). However, only a small fraction of tobacco and alcohol users develop the disease suggesting that genetic factors may play a key role in HNC. Increasing evidence indicate that mTOR is a central regulator of cell growth, proliferation, survival and dysregulation of the PI3K/Akt/mTOR signaling pathway that occurs in many tumors including head and neck cancer. The TSC complex (TSC1/TSC2) negatively regulates mTOR by inhibiting a small GTP binding protein, Rheb, considered to be the direct activator of mTOR. On the other hand, the Ras protein upregulates PI3K signaling which is an upstream effector of mTOR. When PI3K activates Akt, the dual function phosphatase PTEN negatively regulates it. Human cancers frequently harbor activating mutations in the p110 catalytic subunit of PI3K or genomic amplification of Akt. Activated Akt also promotes survival under conditions of cellular stress. In this study we investigated the expression of the critical genes (mTOR, K-ras, PI3KCA, TSC1, RHEB, PTEN and AKT1) acting in this pathway. For this purpose, we analyzed expression levels of these genes in 49 matched HNC tumor and non-cancerous tissue samples by quantitative RT-PCR. We observed a significant downregulation of the mTOR (p=0.005), TSC1 (p=0.001), and PTEN (p=0.000) mRNA expressions. On the other hand, a slight decrease was also observed in K-ras, Akt1 and PI3KCA mRNA levels in tumor tissues compared to the non-cancerous ones. However, the difference in the expression levels of these genes between the two groups were not statistically significant. Whereas we didn9t observe any difference in Rheb mRNA expression level in tumor tissue when compared to the non-cancerous tissue samples. mTOR, TSC1, and PTEN mRNA expression levels were decreased 0.48, 0.44 and 0.32 % in HNC tumor tissue samples compared to non-cancerous tissue samples, respectively . Our result indicate that, the PI3K pathway has an important function in HNC progression with the contribution of more than one gene of this pathway. Citation Format: Nur Buyru, Seda Ekizoglu, Emin Karaman, Ozgun Enver. Expression analysis of PI3K pathway genes in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1800. doi:10.1158/1538-7445.AM2013-1800 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.