title: Thyroid hormone receptors and cancer.
abstract: BACKGROUND
  Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that mediate the actions of the thyroid hormone (T3) in development, growth, and differentiation. The THRA and THRB genes encode several TR isoforms that express in a tissue- and development-dependent manner. In the past decades, a significant advance has been made in the understanding of TR actions in maintaining normal cellular functions. However, the roles of TRs in human cancer are less well understood. The reduced expression of TRs because of hypermethylation, or deletion of TR genes found in human cancers suggests that TRs could function as tumor suppressors. A close association of somatic mutations of TRs with human cancers further supports the notion that the loss of normal functions of TR could lead to uncontrolled growth and loss of cell differentiation.
  
  
  METHODS
  In line with the findings from association studies in human cancers, mice deficient in total functional TRs (Thra1(-/-)Thrb(-/-) mice) or with a targeted homozygous mutation of the Thrb gene (denoted PV; Thrb(PV/PV) mice) spontaneously develop metastatic thyroid carcinoma. This review will examine the evidence learned from these genetically engineered mice that provided strong evidence to support the critical role of TRs in human cancer.
  
  
  CONCLUSIONS
  Loss of normal functions of TR by deletion or by mutations could contribute to cancer development, progression and metastasis.
  
  
  CONCLUSIONS
  Novel mechanistic insights are revealed in how aberrant TR activities lead to carcinogenesis. Mouse models of thyroid cancer provide opportunities to identify molecular targets as potential treatment modalities. This article is part of a Special Issue entitled Thyroid hormone signalling.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Won Gu
authors.initials: WG
authors.lastname: Kim
authors.forename: Sheue-yann
authors.initials: SY
authors.lastname: Cheng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism
chemical_list: D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones