Elucidation of the mechanism underlying thyroid carcinogenesis by galectin-3 overexpression, Development of thyroid-specific galectin-3-transgenic mice

阐明半乳糖凝集素3过度表达导致甲状腺癌发生的机制，开发甲状腺特异性半乳糖凝集素3转基因小鼠

• 批准号: 13671777
• 负责人: INOHARA Hidenori
• 金额: $ 2.24万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671777/
• 关键词: galectin-3; thyroid cancer; throglobulin promoter; transgcnic mice

Galectin-3, a beta-gatacloside-binding lectin, is constitutively overexpressed in thyroid carcinomas of fotlicular cellorigin, whereas neither normal thyroid tissue, benign thyroid adenomatous goiter, nor thyroid follicular adenoma express a detectable amount of galectin-3. Galectin-3 is presumed to be involved in the thyroid carcinogenesis, themechanism underlying which remains largely unknown. The present study aims to develop thyroid-specific galectin-3 transgenic mice in order to give an insight into the thyroid carcinogenesis by overexpression of galectin-3. To this end, we have used the thyroglobulin gene promoter to drive the thyroid folticular cell overexpression of galectin-3 in transgenic mice. The overexpressed galectin-3 is functionally active when driven in this fashion, because it has conferred malignant phenotype on rat normal thyroid follicular cells FRTL-5. FRTL-5 cells overexpressing galectin-3 shows an anchorage-independent growth, which is not observed in either vehicle control or wild type cells. Three transgenic lines have been finally established, all of which express a high level of galectin-3 in the thyroid. These transgenic lines are under breeding, and will be subject to the examination of the pathogenesis of thyroid malignancies in near future.

Galectin-3是一种β-Gatacloside结合凝集素，在甲状腺细胞起源的甲状腺癌中呈结构性过表达，而正常甲状腺组织、良性甲状腺腺瘤性甲状腺肿和甲状腺滤泡性腺瘤都不表达Galectin-3。Galectin-3被认为与甲状腺癌的发生有关，其机制目前仍不清楚。本研究旨在建立甲状腺特异的Galectin-3转基因小鼠，以深入了解Galectin-3过表达在甲状腺癌发生中的作用。为此，我们使用甲状腺球蛋白基因启动子在转基因小鼠中驱动甲状腺叶细胞Galectin-3的过表达。当以这种方式驱动时，过表达的Galectin-3具有功能活性，因为它已经赋予了大鼠正常甲状腺滤泡细胞FRTL-5恶性表型。过量表达Galectin-3的FRTL-5细胞表现出锚定非依赖性生长，这在载体对照组和野生型细胞中都没有观察到。最终建立了三个转基因株系，它们都在甲状腺中表达高水平的Galectin-3。这些转基因株系正在培育中，不久的将来将接受甲状腺恶性肿瘤发病机制的检查。