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[Cancer Research 61, 6105-6111, August 15, 2001]
© 2001 American Association for Cancer Research

Endocrinology

Overexpression and Overactivation of Akt in Thyroid Carcinoma1

Matthew D. Ringel2, Nicole Hayre, Jun Saito, Bertrand Saunier, Frank Schuppert, Henry Burch, Victor Bernet, Kenneth D. Burman, Leonard D. Kohn and Motoyasu Saji

Washington Hospital Center and MedStar Research Institute, Washington, DC 20010 [M. D. R., N H., K. D. B., M S.]; Edison Biotechnology Institute and Ohio University, Athens, Ohio 45701 [J. S., B. S., L. D. K.]; Department of Internal Medicine II, Hospital Bad Oeynhausen, 32545 Bad Oeynhausen, Germany [F. S.]; and Walter Reed Army Medical Center, Washington, DC 20037 [H. B., V. B.]

Enhanced activation of Akt occurs in Cowden’s disease, an inherited syndrome of follicular thyroid, breast, colon, and skin tumors, via inactivation of its regulatory protein, PTEN. Whereas PTEN inactivation is uncommon in sporadic thyroid cancer, activation of growth factor pathways that signal through 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 benign and malignant thyroid tissue for total Akt activation and isoform-specific Akt expression. In thyroid cancer cells, Akt 1, 2, and 3 proteins were expressed, total Akt was activated by insulin phosphatidylinositol 3'-kinase, and inhibition of phosphatidylinositol 3'-kinase reduced cell viability. In human thyroid tissue, increased levels of phosphorylated total Akt were identified in follicular but not papillary cancers compared with normal tissue. Levels of Akt 1 and 2 proteins and Akt 2 RNA were elevated only in the follicular cancers. In paired samples, Akt 1, 2, 3, and phospho-Akt levels were higher in five of six cancers, including three of three follicular cancers. These data suggest that Akt activation may play a role in the pathogenesis or progression of sporadic thyroid cancer.




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