Strucure and function of rat sodium/iodide symporter gene and its expression mechanism in the thyroid

大鼠钠/碘同向转运蛋白基因的结构、功能及其在甲状腺中的表达机制

• 批准号: 09671037
• 负责人: ENDO Toyoshi
• 金额: $ 1.92万
• 依托单位: Yamanashi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671037/
• 关键词: thyroid gland; sodium; iodide symporter; gene expression; thyroid cancer; thyroid transcription factor-1; thyrotropin

Iodide transport into the thyrocytes is the first step of the hormonogenesis and is important for diagnosis and treatment of various thyroid disease. To clarify these, we have cloned rat and human NIS gene and analyzed its structure and function of 5'-flanking region. As the results, we found that (1) the human NIS is a single copy gene mapped at No 19 chromosome (2) expression of NIS gene is stimulated by thyrotropin (TSH) (3) -291 to -134 bp (A in ATG codon is designated as +1) is important for its expression in the thyroid, and -420 to -370 bp is TSH-responsive element (4) thyroid transcription factor-1 (TTF-1) binds to -240 to -237 bp and stimulates NIS gene expression in the thyroid (5) unidentified but novel thyroid specific transcription factor binds to the -420 to -370 bp and might confers to the stimulation of NIS gene expression by TSH (6) NIS gene expression in thyroid cancer tissues is more higher than that in the normal surrounding tissues.These results might contribute to further understanding of iodide transport mechanism in the thyroid, especially in the thyroid cancer tissues, and also important for the diagnosis and treatment of various thyroid disease.

碘离子转运入甲状腺细胞是甲状腺发生的第一步，对甲状腺疾病的诊断和治疗具有重要意义。为了阐明这些，我们克隆了大鼠和人NIS基因，并分析了其5 '-侧翼区的结构和功能。结果表明：（1）NIS基因是一个单拷贝基因，定位于19号染色体上;（2）NIS基因的表达受促甲状腺激素（TSH）的刺激;（3）-291 ~-134bp（ATG密码子中的A指定为+1）对于其在甲状腺中的表达是重要的，甲状腺转录因子-1（TTF-1）与-240至-237 bp结合并刺激甲状腺中NIS基因的表达;（6）NIS基因在甲状腺癌组织中的表达明显高于癌旁正常组织，这一结果有助于进一步了解甲状腺尤其是甲状腺癌组织中碘离子的转运机制，对甲状腺疾病的诊断和治疗具有重要意义。

项目成果

Ohmori,M.et al.: "A novel thyroid transcription factor is essential for thyrotropi-induced upregulation of Na/I symporter gene expression." Molecular Endocrinology. 12. 727-736 (1998)

Ohmori,M.等人：“一种新型甲状腺转录因子对于促甲状腺激素诱导的 Na/I 同向转运蛋白基因表达的上调至关重要。”

Endo,T.et al.: "Thyroid Transcription Factor-1 Activates the Promoter Activity of Rat Thyroid Na^+/I^- Symporter Geen" Mol.Endocrinol.11. 1747-1755 (1997)

Endo,T.et al.：“甲状腺转录因子-1 激活大鼠甲状腺 Na^ /I^- Symporter Geen 的启动子活性”Mol.Endocrinol.11。

Ohmori, M.et al.: "A novel thyroid transcription factor is essential for thyrotropi-induced up-regulation of Na/l symporter gene expression." Molecular Endocrinology. 12. 727-736 (1998)

Ohmori, M.等人：“一种新型甲状腺转录因子对于促甲状腺激素诱导的 Na/l 协同转运蛋白基因表达的上调至关重要。”

Ohmori M.et al.: "A novel thyroid transcription factor is essential for thyrotropin-induced up-regulation of Na/I symporter gene expression." Molecular Endocrinology. 12. 727-736 (1998)

Ohmori M.等人：“一种新型甲状腺转录因子对于促甲状腺素诱导的 Na/I 同向转运蛋白基因表达的上调至关重要。”

Saito,T.et al.: "Increased Expression of Na^+/I^- Symporter in Papillary Thyroid Carcinoma" J.Clin.Invest.(in press). (1998)

Saito,T.et al.：“甲状腺乳头状癌中Na^/I^-同向转运蛋白的表达增加”J.Clin.Invest.（出版中）。