Molecular and pathologic study on functional and regulation of thyroid tumors

甲状腺转录因子-1(TTF-1)是1990年发现的一种甲状腺特异转录因子，是一种含有同源结构域的蛋白质，负责甲状腺特异基因、甲状腺球蛋白、甲状腺过氧化物酶和促甲状腺激素受体的转录激活。几位作者对TTF-1的结构和功能进行了研究。我们用免疫组织化学方法研究了甲状腺转录因子-1(TTF-1)在正常甲状腺滤泡细胞和滤泡细胞来源的甲状腺良恶性肿瘤中的核定位。然而，我们未能在未分化的癌细胞中证明TTF-1。TTF-1mRNA原位杂交结果支持免疫组织化学结果。分子方法、Northern杂交和RT-PCR分析表明，TTF-1mRNA不仅在正常甲状腺组织中表达，而且在不同组织学类型的甲状腺肿瘤中也有表达。有趣的是，TTF-1在正常滤泡旁细胞(C细胞)和来源于C细胞的甲状腺髓样癌中也有表达。结果表明，TTF-1在甲状腺滤泡细胞和C细胞的激素发生机制中起重要作用，结合该转录因子的分子检测和病理检查有助于了解甲状腺肿瘤的生理本质和甲状腺疾病的病理诊断。

Thyroid transcription factor-1 (TTF-1), as recognized in 1990, is a thyroid specific transcription factor that is a homeodomain-containing protein responsible for transcriptional activation of thyroid-specific genes, thyroglobuline, thyroperoxidase, and thyrotropin receptor. The structure and function of TTF-1 have been investigated by several authors. However, little is known about the expression in diseased thyroid tissues.We investigated the expression of thyroid transcription factor-1 (TTF-1) using immunohistochemistry and demonstrated the nuclear localization of TTF-1 in normal follicular cells and follicular cell derived benign and malignant thyroid tumors. However, we failed to demonstrate TTF-1 in undifferentiated carcinoma cells. In situ hybridization for TTF-1mRNA supported the immunohistochemical results. Molecular methods, Northern blotting and RT-PCR analyses, revealed that expression of TTF-1mRNA was demonstrated not only in normal thyroid tissues but also in various histologic types of thyroid tumors.Interestingly, TTF-1 expression was evident in normal parafollicular cells (C cells) and medullary thyroid carcinomas derived from C cell. Immunohistochemistry for TTF-1 and in situ hybridization for TTF-1 mRNA supported these results.From our results, TTF-1 plays important roles in hormonogenetic mechanism in thyroid follicular cells and C cells and molecular examinations in conjunction with pathologic examinations for this transcriptional factor can be useful in understanding of physiological nature of thyroid tumors and in pathologic diagnosis of thyroid diseases.