PI3K/mTOR Pathway is Active in Head and Neck Squamous Cell Carcinoma

Objectives: mTOR signaling pathway is an important regulator of cell proliferation, survival, and motility. The gain or loss of function of proteins related to this pathway results in the neoplastic transformation in several types of cancers. The objective of this study was to evaluate the immunohistochemical expression of mTOR pathway proteins in patients with head and neck squamous cell carcinoma (HNSCC) and analyze the expression of protein mTOR in HNSCC cell lines treated with inhibitors of mTOR.
Methods: This study analyzed twenty-eight tissue samples from patients with HNSCC were evaluated. The material was obtained from tissue removed for biopsy, fixed in formalin and immersed in paraffin. The proteins analyzed were PI3K, AKT, pmTOR (Ser 2448) and PTEN. The analysis of immunohistochemical expression was performed by a semi-quantitative assessment. HNSCC cell lines, FADU and SCC9, were treated with mTOR inhibitors Everolimus and Temsirolimus, and the pathways modulation was accessed using Western Blot.
Results: High levels of PI3K were found in 85.7% of HNSCC. Sixty-six percent of the cases were positive for AKT and 64.3% for the p-mTOR. PTEN loss was observed in 50% of studied tumors. It was observed decreased expression of mTOR and p-mTOR proteins in FADU and SCC9 cell lines after treatment with Temsirolimus and Everolimus.
Conclusions: Although the results of this study are still preliminary, they suggest that there may be a direct association between expression of mTOR pathway proteins (PI3K, AKT, and mTOR) and HNSCC. The loss of PTEN expression may be as well associated with the increased expression of proteins PI3K, AKT, and mTOR. Furthermore, in vitro experiments suggests that Temsirolimus and Everolimus are effective to inhibit the expression of the mTOR protein in HNSCC cell lines.