title: Deiodination in cancer growth: the role of type III deiodinase.
abstract: Thyroid hormone (TH) is a pleiotropic agent that has widespread biological functions, i.e., it controls cellular growth, tissue development and homeostasis and neoplastic transformation. Suitable TH levels are critical for the development of various types of tissues and are essential for the regulation of metabolic processes throughout life. The serum concentrations of TH affect its biological activity. Moreover, at tissue level, TH action is regulated by the expression and activity of deiodinases, i.e., the enzymes that mediate the metabolic pathways by activating and/or inactivating TH. The type I and II deiodinases (D1 and D2) initiate TH action by converting thyroxine (T4) into the active TH form (T3), whereas type III deiodinase (D3) mediates the local attenuation of TH by converting T4 and T3 into the inactive metabolites rT3 and T2, respectively. The deiodinase system is a potent mechanism of pre-receptoral control of TH action; it is often altered in such pathological conditions as cancer. D3 is widely expressed in embryonic tissues and in placenta, where it blocks excessive maternal-to-fetal transfer of TH. In contrast, during late neonatal and adult life, D3 is expressed mainly in the central nervous system and skin. Interestingly, D3 expression is re-activated in various types of human cancers. Here we review recent evidence that D3 expression plays a crucial role in human carcinogenesis, and speculate as to its complex role in the regulation of cell proliferation in several neoplastic contexts. It is conceivable that the local modulation of TH action via deiodinases is a powerful molecular tool to manipulate the intracellular TH status, thus influencing the growth and maintenance of selected hormone-dependent cancers.
authors.affiliation: Department of Molecular and Clinical Endocrinology and Oncology, University of Naples "Federico II", Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sibilio
authors.forename: R
authors.initials: R
authors.lastname: Ambrosio
authors.forename: C
authors.initials: C
authors.lastname: Bonelli
authors.forename: M A
authors.initials: MA
authors.lastname: De Stefano
authors.forename: V
authors.initials: V
authors.lastname: Torre
authors.forename: M
authors.initials: M
authors.lastname: Dentice
authors.forename: D
authors.initials: D
authors.lastname: Salvatore
mesh_terms: D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D004789:Enzyme Activation; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology / Q000503:physiopathology; D007453:Iodide Peroxidase / Q000235:genetics / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000502:physiology*; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000473:pathology; D009928:Organ Specificity; D013347:Subcellular Fractions / Q000201:enzymology; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism; D014285:Triiodothyronine, Reverse / Q000096:biosynthesis
chemical_list: D009363:Neoplasm Proteins; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D013974:Thyroxine