PIK3CA and thyroid cancer, nonmedullary, 2: 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).