Novel Oncogenic Actions of TRβ Mutants in Tumorigenesis

The thyroid hormone, T3, plays important roles in metabolism, growth, and differentiation. Germline mutations in thyroid hormone receptor beta (TR beta) have been identified in many individuals with resistance to thyroid hormone, a syndrome of reduced sensitivity to T3. A close association of somatic mutations of TR beta with several human cancers has become increasingly apparent, but how TR beta mutants could be involved in the carcinogenesis in vivo has not been addressed. The creation of a mouse model (TR beta(PV/PV) mouse) that harbors a knockin mutation of TR beta (denoted TR beta PV) has facilitated the study of the molecular actions of TR beta mutants in vivo. The striking phenotype of thyroid cancer and the development of pituitary tumors exhibited by TR beta(PV/PV) mice have uncovered novel functions of a TR beta mutant in tumorigenesis. It led to the important findings that the oncogenic action of TR beta PV is mediated by both genomic and nongenomic actions to after gene expression and signaling, pathways activity. (C) 2009 IUBMB IUBMB Life, 61(5): 528-536, 2009