ABSTRACT
PI3K/Akt Pathways ................................................................................................................. 31 3.5 Aberrant Methylation of Genes around the MAP Kinase and PI3K/Akt Pathways .............. 32 3.6 Impaired Iodide Metabolism Coupled to Aberrant MAP Kinase and PI3K/Akt Signaling .. 33 3.7 Summary ................................................................................................................................34 References ........................................................................................................................................ 35
TPO Thyroperoxidase TSH Thyroid-stimulating hormone TSHR TSH receptor VEGF Vascular epithelial growth factor
ABSTRACT: Remarkable progress has occurred in recent years in understanding the molecular derangements in major signaling pathways in thyroid cancer, particularly genetic and epigenetic alterations in the MAP kinase and PI3K/Akt pathways. The previously established Ras and RET/ PTC mutations and the recently discovered BRAF mutation (V600E) play a fundamental role in thyroid tumorigenesis through MAP kinase pathway activation. The prevalent and oncogenically potent BRAF mutation plays a unique role, particularly in promoting the aggressiveness of papillary thyroid cancer. Genetic alterations, such as mutations in the genes for Ras, PIK3CA, PTEN, and receptor tyrosine kinases, and genomic ampliˆcations of some of these genes are also common, which play their roles in thyroid tumorigenesis through aberrantly activating the PI3K/Akt pathway. Consequent or associated epigenetic alterations, such as aberrant methylation of tumor suppressor and thyroid-speciˆc genes, are also common in the molecular pathogenesis of thyroid cancer, including aberrant silencing of thyroid genes and resultant loss of radioiodine avidity of thyroid cancer. These genetic and epigenetic alterations in the two major signaling pathways provide a strong basis for the current development of novel molecular-based diagnostic, prognostic, and therapeutic strategies for thyroid cancer.
