Distribution of Tsc1 protein detected by immunohistochemistry in various normal rat tissues and the renal carcinomas of Eker rat: Detection of limited colocalization with Tsc1 and Tsc2 gene products in vivo
Distribution of Tsc1 protein detected by immunohistochemistry in various normal rat tissues and the renal carcinomas of Eker rat: Detection of limited colocalization with Tsc1 and Tsc2 gene products in vivo
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DOI：
10.1038/labinvest.3780143
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发表时间：
2000-09-01
影响因子：
5
通讯作者：
Hino, O
中科院分区：
文献类型：
--
作者：
Fukuda, T;Kobayashi, T;Hino, O
我们和其他研究人员先前证明，大鼠结节性硬化症基因（Tsc2）同源基因的遗传突变和随后的二次打击是导致Eker肾癌（RC）的原因。在人类中，已知TSC2基因的改变会导致结节性硬化症复合体（TSC），导致多个器官的错构瘤病变，但TSC2的功能尚不完全清楚。近年来，另一个与人类TSC有关的基因（TSC1）被克隆出来，并报道了TSC1与TSC2蛋白之间的结合。本研究通过免疫组化检测Tsc1蛋白的表达，并与Tsc2蛋白的表达进行比较，明确了Tsc蛋白在体内的相关性。Tsc1蛋白在神经系统和许多内分泌组织中表达，包括胰岛、甲状旁腺、睾丸和卵巢。在肾、子宫、小肠、大肠、肝脏等多个器官的上皮组织中也检测到Tsc1。我们的结果表明，Tsc1和Tsc2蛋白的器官分布重叠，但不相同。在细胞内分布，双荧光免疫标记可以确定在某些器官中只有部分Tsc1信号与Tsc2重叠。这些结果表明在内源性表达中存在Tsc蛋白的共定位和独立形式。此外，在Tsc2突变体（Eker）大鼠的RC中检测到相对较高的Tsc1蛋白表达。
We and others previously demonstrated that hereditary mutation and a subsequent second hit in the rat homolog of tuberous sclerosis gene (Tsc2) are responsible for Eker renal carcinomas (RC). in humans, alteration in the TSC2 gene is known to cause the tuberous sclerosis complex (TSC) that results in hamartomatous lesions in multiple organs, but the function of TSC2 is not fully understood. In recent years, a second gene (TSC1) responsible for human TSC has been cloned, and binding between TSC1 and TSC2 proteins was reported. In this study, to clarify associations between Tsc proteins in vivo, the expression of Tsc1 protein was detected by immunohistochemistry, and compared with Tsc2 expression. Tsc1 protein was expressed in the nervous system and in many endocrine tissues, including pancreatic islets, the parathyroids, testis, and ovary. Tsc1 was also detected in the many epithelial tissues of organs, such as kidney, uterus, small and large intestine, and liver. Our results indicate overlapping, but not identical, organ distributions of Tsc1 and Tsc2 proteins. At the intracellular distribution, double fluorescent immunolabeling allowed the determination that only a partial portion of Tsc1 signals overlapped with Tsc2 in some organs. These results suggest the existence of co-localizing and independent forms of Tsc proteins in endogenous expressions. Additionally, relatively high expression of Tsc1 protein was detected in RC in the Tsc2 mutant (Eker) rat.