Overexpression and overactivation of Akt in thyroid carcinoma

Enhanced activation of Akt occurs in Cowden's disease, an inherited syndrom e of follicular thyroid, breast, colon, and skin tumors, via inactivation o f its regulatory protein, PTEN. Whereas PTEN inactivation is uncommon in sp oradic thyroid cancer, activation of growth factor pathways that signal thr ough Akt is frequently identified. We hypothesized that Akt overactivation could be a common finding in sporadic thyroid cancer and might be important in thyroid cancer biology. We examined thyroid cancer cells lines and beni gn and malignant thyroid tissue for total Akt activation and isoform-specif ic Akt expression. In thyroid cancer cells, Akt 1, 2, and 3 proteins were e xpressed, total Akt was activated by insulin phosphatidylinositol 3 ' -kina se, and inhibition of phosphatidylinositol 3 ' -kinase reduced cell viabili ty. In human thyroid tissue, increased levels of phosphorylated total Akt w ere identified in follicular but not papillary cancers compared with normal tissue. Levels of Akt I and 2 proteins and Akt 2 RNA were elevated only in the follicular cancers. In paired samples, Akt 1, 2, 3, and phospho-Akt le vels were higher in five of six cancers, including three of three follicula r cancers. These data suggest that Akt activation may play a role in the pa thogenesis or progression of sporadic thyroid cancer.