Increased expression of phosphorylated p70S6 kinase and akt in papillary thyroid cancer tissues
Increased expression of phosphorylated p70S6 kinase and akt in papillary thyroid cancer tissues
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DOI：
10.1507/endocrj.50.77
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发表时间：
2003-02-01
影响因子：
2
通讯作者：
Takano, K
中科院分区：
文献类型：
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作者：
Miyakawa, M;Tsushima, T;Takano, K
虽然一些异常的癌基因已被报告在甲状腺肿瘤，很少有信息是关于信号转导通路参与甲状腺肿瘤细胞的生长。p70 S6激酶（p70 S6 K）和Akt都是磷脂酰肌醇3激酶（PI 3 K）下游的激酶。这些激酶被甲状腺细胞中的生长因子包括IGF-1、EGF/TGF-α和HGF磷酸化和激活。由于据报道这些生长因子的受体在人甲状腺癌中过表达，我们假设PI 3 K介导的信号传导在甲状腺癌中过度活化。采用Western blot方法检测20例甲状腺乳头状癌患者癌组织及癌旁正常组织中p70 S6 K和Akt的表达。与正常甲状腺组织（N）相比，肿瘤组织（T）中p70 S6 K的蛋白水平表达增加，并且与周围正常组织相比，肿瘤中磷酸化p70 S6 K的表达也显著增加。免疫组化进一步证实p70 S6 K在肿瘤组织中的过表达。在大多数情况下，甲状腺癌细胞的胞质中可见强免疫反应，而在周围正常部分中发现很少的免疫反应。磷酸化Akt（pAkt）在肿瘤组织中的表达也显著升高。Akt的底物Bad磷酸化（pBad）在肿瘤组织中也与Akt的活化相关，并且pAkt的T/N比与pBad的T/N比呈正相关。本文提供的数据表明，p70 S6 K和Akt在大多数人乳头状癌细胞中均被激活。这些信号的激活可能通过刺激细胞增殖和/或阻止细胞凋亡而参与乳头状癌的进展。
Although a number of abnormalities in oncogenes have been reported in thyroid neoplasms, little information is available on the signal transduction pathway involved in neoplastic thyroid cell growth. Both p70S6 kinase (p70S6K) and Akt are kinases downstream of phosphatidylinositol 3 kinase (PI3K). These kinases are phosphorylated and activated by growth factors including IGF-1, EGF/TGF-alpha, and HGF in thyroid cells. Since the receptors for these growth factors are reportedly overexpressed in human thyroid cancer, we hypothesized that the PI3K-mediated signalings are overactivated in thyroid cancers. Tumorous and adjacent normal tissues of 20 patients with papillary thyroid cancer were obtained at surgery, and expression of p70S6K and Akt were measured by Western blot. Expression of the protein levels of p70S6K was increased in tumor tissues (T) compared to normal thyroid tissues (N), and expression of phosphorylated p70S6K was also significantly increased in tumor than in surrounding normal tissues. Overexpression of p70S6K in tumor tissues was further confirmed by immunohistochemistry. Strong immunoreactivity in the cytoplasm of thyroid cancer cells was seen in the majority of cases, whereas little immunoreactivity was found in the surrounding normal portion. Expression of phosphorylated Akt (pAkt) was also significantly higher in tumor tissues. Phosphorylation of Bad (pBad), a substrate of Akt, was also increased in the tumor tissues in association with activation of Akt, and the T/N ratio for pAkt positively correlated to the T/N ratio for pBad. The data presented here demonstrate that both p70S6K and Akt are activated in the majority of human papillary cancer cells. Activation of these signalings may be involved in the progression of papillary carcinoma by stimulating cell proliferation and/or preventing apoptosis.