荧光素酶
碘化钠转运体
癌症研究
转基因小鼠
转基因
生物
强力霉素
报告基因
甲状腺癌
甲状腺癌
MAPK/ERK通路
甲状腺
癌基因
基因表达
内分泌学
内科学
医学
癌症
转染
基因
磷酸化
细胞生物学
共转运蛋白
遗传学
细胞周期
运输机
抗生素
作者
Katherine A. B. Knostman,Anjli Venkateswaran,Brian Zimmerman,Charles C. Capen,Sissy Jhiang
出处
期刊:Thyroid
[Mary Ann Liebert]
日期:2007-12-01
卷期号:17 (12): 1181-1188
被引量:14
标识
DOI:10.1089/thy.2007.0224
摘要
Background: RET/PTC1 chromosomal rearrangement is associated with papillary thyroid carcinoma formation in children exposed to ionizing radiation. We previously created a transgenic mouse model with thyroid-targeted constitutive RET/PTC1 expression and demonstrated papillary thyroid carcinoma formation. Objective: In this study, we aimed to create a doxycycline-inducible mouse model of thyroid RET/PTC1 and luciferase reporter gene coexpression to allow for noninvasive monitoring of transgene expression in mice of various ages and timepoints after induction. Design: Transgenic mice carrying the rtTA gene driven by the thyroglobulin promoter were generated, and crossed with responder mice carrying RET/PTC1 and firefly luciferase genes under control of a bidirectional tetracycline response element. Main outcomes: Most bitransgenic mice had thyroid-targeted, doxycycline-independent transgene expression. Only one line had thyroid-targeted, doxycycline-regulated RET/PTC1 and luciferase coexpression, in which doxycycline induction of RET/PTC1 led to Erk phosphorylation and reduced expression of the sodium/iodide symporter (NIS). However, thyroid lesions were not found in any bitransgenic mice examined. Conclusions: We found that acute RET/PTC1 expression can activate the MEK/Erk pathway and downregulate NIS expression in the mouse thyroid gland. However, a higher level of RET/PTC1 is likely necessary for tumor formation. Thyroid luciferase induction was detectable noninvasively using IVIS™ in vivo imaging.
科研通智能强力驱动
Strongly Powered by AbleSci AI