Akt1 deficiency delays tumor progression, vascular invasion, and distant metastasis in a murine model of thyroid cancer

Akt activation is common in progressive thyroid cancer. In breast cancer, Akt1 induces primary cancer growth, but is reported to inhibit metastasis in vivo in several model systems. In contrast, clinical and in vitro studies suggest a metastasis-promoting role for Akt1 in thyroid cancer. The goal of this study was to determine the functional role of Akt1 in thyroid cancer growth and metastatic progression in vivo using thyroid hormone receptor (TR) β PV/PV knock-in (PV) mice, which develop metastatic thyroid cancer. We crossed Akt1 −/− and PV mice and compared tumor development, local progression, metastasis and histology in TRβ PV/PV /Akt1 +/+ (PVPV-Akt1WT) and TRβ PV/PV /Akt1 −/− (PVPV-Akt1KO) mice. Mice were killed at 3, 6, 9, 12 and 15 months; necropsy was performed and serum thyroid stimulating hormone (TSH) was measured. Thyroid hyperplasia occurred in both groups beginning at 3 months; the thyroid size was greater in the PVPV-Akt1WT mice ( P