While PI3K pathways have a crucial function in balancing homeostasis in thyroid hyperplasia, FTC occurring in thyroid-specific PTEN –/– models demonstrate that constitutive PI3K signaling activation is not sufficient for tumor transformation, and that a synergistic effect with PTEN and KRAS oncogenic allele deletion is required to lead to rapid development of thyroid follicular carcinoma (37). This evidence concerns the gene PTEN and thyroid cancer, nonmedullary, 2.