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

半乳糖凝集素-3是一种β -加糖苷结合的凝集素，在滤泡细胞源性甲状腺癌中组成性过表达，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均未表达可检测到的半乳糖凝集素-3。半乳糖凝集素-3被认为与甲状腺癌的发生有关，其潜在的机制仍不清楚。本研究旨在建立甲状腺特异性的半乳糖凝集素-3转基因小鼠，以深入了解半乳糖凝集素-3过表达在甲状腺癌变中的作用。为此，我们利用甲状腺球蛋白基因启动子驱动转基因小鼠甲状腺滤泡细胞过表达半乳糖凝集素-3。当以这种方式驱动时，过度表达的半乳糖凝集素-3在功能上是活跃的，因为它赋予大鼠正常甲状腺滤泡细胞FRTL-5恶性表型。过表达半乳糖凝集素-3的FRTL-5细胞表现出不依赖于锚定的生长，这在对照和野生型细胞中都没有观察到。最终建立了三个转基因系，它们都在甲状腺中表达高水平的半乳糖凝集素-3。这些转基因系正在进行育种，并将在不久的将来接受甲状腺恶性肿瘤发病机制的研究。

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.