Abstract

Among thyroid cancer papillary thyroid carcinoma is the most widely met? The loss of thyroid-specific functions during tumor progression determines the resistance of thyroid tumors to traditional radioiodine therapy. Specific drugs for aggressive and metastatic thyroid cancer are required for the development of effective therapy. Tyrosine kinase inhibitors (TKIs) are emerging as new tool for aggressive thyroid cancer. Over expression of MET (mesenchymal epithelial transition) receptor is found in papillary thyroid carcinoma. We aimed to study the phosphorylation of MET in the tissue of papillary thyroid carcinoma and effect of a TKI genistein on this process. The thyroid homogenates were incubated with genistein (Sigma-Aldrich, Germany) and then the phosphorylated MET was determined by Phospho-MET ELISA Kit (Sigma-Aldrich, Germany). In our studies, genistein at the concentrations of 10 and 20μM reduced receptor phosphorylation by 25.1% and 18.3%, respectively. The native serum of the patient with papillary carcinoma increased phosphorylation of MET by 44.6%. Our results provide data that genistein suppresses phosphorylation of MET in tissue of thyroid cancer in physiological doses. The effect of genistein on MET receptor, responsible for mesenchymal-epithelial transition, indicates its anti-metastatic properties.

Keywords: Thyroid Carcinoma, Tyrosine Kinase, MET Receptor, Phosphorylation, Genistein.

Abbreviations

TKIs: Tyrosine Kinase Inhibitors; MET: Mesenchymal Epithelial Transition; HGF: Hepatocyte Growth Factor; DTC: Differentiated Thyroid Carcinoma; PTC: Papillary Thyroid Cancer; FTC: Follicular Thyroid