The C-terminal domain of the adenomatous polyposis coli (Apc) protein is involved in thyroid morphogenesis and function
The C-terminal domain of the adenomatous polyposis coli (Apc) protein is involved in thyroid morphogenesis and function
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腺瘤性结肠息肉病 (Apc) 蛋白的 C 端结构域参与甲状腺形态发生和功能
DOI：
10.1007/s00795-010-0529-9
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发表时间：
2011
影响因子：
1.8
通讯作者：
Takao Senda
中科院分区：
文献类型：
--
作者：
Atsushi Yokoyama;Ryuji Nomura;Masafumi Kurosumi;Atsushi Shimomura;Takanori Onouchi;Akiko Iizuka-Kogo;Ron Smits;Riccardo Fodde;Mitsuyasu Itoh;Takao Senda
结肠腺瘤性息肉病(APC)是一种多功能蛋白，也是一种肿瘤抑制因子。为了确定APC的C-末端结构域的功能，我们研究了Apc1638T/1638T小鼠，它们表达的是一个缺失C-末端结构域的截短的APC。Apc1638T/1638T小鼠没有肿瘤，并且表现出生长迟缓。本研究分析了Apc1638T/1638T小鼠甲状腺的形态和功能。Apc1638T/1638T和Apc+/+小鼠血清甲状腺激素基础浓度无显著差异。Apc1638T/1638T小鼠的甲状腺滤泡大小显著大于Apc+/+小鼠。注射外源性促甲状腺激素(TSH)后，Apc1638T/1638T小鼠的血清T4升高幅度低于Apc+/+小鼠。TSH还诱导Apc1638T/1638T小鼠比Apc+/+小鼠更显著地缩小甲状腺滤泡大小。免疫组织化学和电子显微镜分析表明，Apc1638T/1638T小鼠的卵泡上皮细胞具有不规则形状的粗面内质网。这些结果表明，APC的C-末端结构域参与了甲状腺的形态和功能。
Adenomatous polyposis coli (APC) is a multifunctional protein as well as a tumor suppressor. To determine the functions of the C-terminal domain of Apc, we have investigatedApc1638T/1638Tmice, which express a truncated Apc that lacks the C-terminal domain.Apc1638T/1638Tmice are tumor free and exhibit growth retardation. In the present study, we analyzed the morphology and functions of the thyroid gland inApc1638T/1638Tmice. There was no significant difference in the basal concentration of serum thyroid hormones betweenApc1638T/1638TandApc+/+mice. Thyroid follicle size was significantly larger inApc1638T/1638Tmice than inApc+/+mice. The extent of serum T4 elevation following exogenous thyroid-stimulating hormone (TSH) injection was lower inApc1638T/1638Tmice than inApc+/+mice. TSH also induced a greater reduction in thyroid follicle size inApc1638T/1638Tmice than inApc+/+mice. Analyses using immunohistochemistry and electron microscopy indicated that follicular epithelial cells inApc1638T/1638Tmice had an enlarged rough endoplasmic reticulum of irregular shape. These results suggest that the C-terminal domain of Apc is involved in thyroid morphology and function.