Department of Biochemistry and Molecular Biology, The Medical Centre of Postgraduate Education, Warsaw, Poland.
J Endocrinol Invest. 2011 Oct;34(9):716-28. doi: 10.3275/7754. Epub 2011 May 27.
Thyroid hormones (TH) regulate key cellular processes, including proliferation, differentiation, and apoptosis in virtually all human cells. Disturbances in TH pathway and the resulting deregulation of these processes have been linked with neoplasia. The concentrations of TH in peripheral tissues are regulated via the activity of iodothyronine deiodinases. There are 3 types of these enzymes: type 1 and type 2 deiodinases are involved in TH activation while type 3 deiodinase inactivates TH. Expression and activity of iodothyronine deiodinases are disturbed in different types of neoplasia. According to the limited number of studies in cancer cell lines and mouse models changes in intratumoral and extratumoral T3 concentrations may influence proliferation rate and metastatic progression. Recent findings showing that increased expression of type 3 deiodinases may lead to enhanced tumoral proliferation support the idea that deiodinating enzymes have the potential to influence cancer progression. This review summarizes the observations of impaired expression and activity in different cancer types, published to date, and the mechanisms behind these alterations, including impaired regulation via TH receptors, transforming growth factor-β, and Sonic-hedgehog pathway. Possible roles of deiodinases as cancer markers and potential modulators of tumor progression are also discussed.
甲状腺激素 (TH) 调节着几乎所有人类细胞中的关键细胞过程，包括增殖、分化和凋亡。TH 途径的紊乱以及由此导致的这些过程的失调与肿瘤发生有关。外周组织中 TH 的浓度通过碘甲状腺原氨酸脱碘酶的活性来调节。这些酶有 3 种类型：1 型和 2 型脱碘酶参与 TH 的激活，而 3 型脱碘酶使 TH 失活。不同类型的肿瘤中，碘甲状腺原氨酸脱碘酶的表达和活性都受到了干扰。根据在癌细胞系和小鼠模型中的为数不多的研究，肿瘤内和肿瘤外 T3 浓度的变化可能会影响增殖率和转移进展。最近的研究结果表明，3 型脱碘酶表达的增加可能导致肿瘤增殖的增强，这支持了脱碘酶有可能影响癌症进展的观点。本综述总结了迄今为止在不同癌症类型中观察到的表达和活性受损的情况，以及这些改变背后的机制，包括通过 TH 受体、转化生长因子-β 和 Sonic-hedgehog 途径的调节受损。还讨论了脱碘酶作为癌症标志物和肿瘤进展潜在调节剂的可能作用。
