甲状腺特异性转录因子对甲状腺功能的调控

甲状腺特异性转录因子是调控甲状腺功能的小分子蛋白,包括甲状腺转录因子(TTF)-1、双链复合蛋白(Pax)-8和TTF-2。生理状态下,促甲状腺激素、胰岛素和胰岛素样生长因子-1通过对TTF-1、TTF-2和Pax-8的表达及活性的调节,上调钠碘同向转运体、甲状腺过氧化物酶、甲状腺球蛋白、促甲状腺激素受体的表达,调节甲状腺功能。Pax-8和TTF-1也可使主要组织相容性复合物Ⅰ表达下调,使甲状腺可以耐受自身激素合成过程中增加的基因产物。TTF-1也可影响人类各组织中5′脱碘酶2型以及甲状腺滤泡旁细胞(C细胞)和甲状旁腺细胞中钙离子转运相关基因的表达。     

Thyroid cancer development and progression: emerging role of cancer stem cells

Thyroid cancer is the most common endocrine malignancy. Although the majority of thyroid cancers are well differentiated and have a favorable prognosis, a minor proportion are poorly differentiated malignancies, which show an aggressive behavior and are refractory to conventional cancer treatments. The molecular mechanisms underlying thyroid development and progression are incompletely understood. Most of thyroid tumorigenesis models propose that thyroid cancer originates from the normal thyrocytes that, via the accumulation of genetic alterations, acquire a malignant phenotype and the ability to metastatize. However, recent progress in clarifying the molecular mechanisms of thyroid embryogenesis/development and the discovery of fetal/stem-like cells within the thyroid gland, have raised the possibility that thyroid cancer originates from progenitor/stem cells. These cells have the ability to self-renew and to undergo multilineage differentiation, and are resistant to common anticancer treatments. Thyroid progenitor/stem cells have been isolated from thyroid cancer and the normal counterpart. Further insights in the biology of these cells will open new perspectives in terms of prevention, diagnosis and therapy of thyroid cancers, especially those with an aggressive behaviour. More effective protocols for the identification and isolation of thyroid cancer stem cells will allow us to specifically and safely target these cells with the aim to definitely eradicate aggressive thyroid cancers.     

Thyroid cancer stem cells

Thyroid cancer is the most frequently diagnosed endocrine cancer and causes more deaths than all other endocrine cancers combined. Research findings support the concept that a subpopulation of thyroid cancer cells displays properties characteristic of stem cells. These putative cancer-forming entities drive tumorigenesis as a result of their dual ability to undergo self-renewal and to differentiate into various types of cancer cells; they also mediate metastasis and are resistant to the effects of chemotherapy and radiation therapy. This Review discusses the cellular origin of thyroid cancer and the properties of the thyroid cancer stem cell niche. The article critically evaluates the methods used to identify molecular markers expressed by thyroid-cancer-initiating cells and outlines prospective therapeutic strategies to directly target these cells. Stem-cell technology offers an unprecedented opportunity to investigate these crucial cancer stem cell populations and to advance understanding of the molecular mechanisms that control disease processes. Such knowledge could potentially lead to the development of more effective and safer treatment regimens for late-stage thyroid cancer than are currently available.