Increased Expression of Cyclin-Dependent Kinase-Interacting Protein p21 during Tamoxifen-Induced Hepatocarcinogenesis in Female Rats
Increased Expression of Cyclin-Dependent Kinase-Interacting Protein p21 during Tamoxifen-Induced Hepatocarcinogenesis in Female Rats
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雌性大鼠他莫昔芬诱导肝癌过程中细胞周期蛋白依赖性激酶相互作用蛋白 p21 表达增加
DOI：
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
M. Degawa
中科院分区：
文献类型：
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作者：
T. Kasahara;C. Kakinuma;Chitose Kuwayama;Masamichi Hashiba;T. Harada;M. Degawa
雌性Sprague-Dawley大鼠被给予单剂量的他莫昔芬（20 mg/kg体重）或相同剂量，间隔24小时，持续2、12或52周，以及细胞周期蛋白依赖性激酶相互作用蛋白p21（p21），肿瘤抑制蛋白p53，并对三苯氧胺诱发肝癌过程中肝脏胎盘型谷胱甘肽S-转移酶（GST-P）进行了比较研究。肝细胞癌的发展仅在给药他莫昔芬52周的大鼠中进行组织病理学观察，但在任何其他实验组中均未观察到。在给予他莫昔芬2周的大鼠中首次观察到p21的mRNA和蛋白水平的显著增加，并且随着进一步的长期治疗，该水平增加。免疫组织化学分析显示，p21和GST-P在大鼠肝脏给药他莫昔芬12周和52周，p21阳性细胞的定位不一定与GST-P阳性细胞相一致。在52周组中，p21阳性细胞，而不是GST-P阳性细胞，观察到优先在组织病理学恶性细胞组成的区域。本研究表明，在他莫昔芬诱导的肝癌发生过程中，p21的mRNA和蛋白表达水平增加。本文还对p21蛋白在肝癌发生过程中表达增高的意义进行了讨论。
Female Sprague-Dawley rats were given a single dose of tamoxifen (20 mg/kg body weight) by gavage or the same dose at 24-hr intervals for 2, 12, or 52 weeks, and the altered expression of cyclin-dependent kinase-interacting protein p21 (p21), tumor suppression protein p53, and the placental form of glutathione S-transferase (GST-P) in the liver was comparatively examined during the process of tamoxifen-induced hepatocarcinogenesis. The development of hepatocellular carcinoma was histopathologically observed only in rats administered tamoxifen for 52 weeks, but not in any other experimental groups. Significant increases in levels of the mRNA and protein of p21 were first observed in rats administered tamoxifen for 2 weeks, and the levels increased with further long-term treatment. Immunohistochemical analyses of p21 and GST-P in the liver of rats administered tamoxifen for 12 and 52 weeks revealed that the localization of p21-positive cells did not necessarily coincide with that of GST-P-positive cells. In the 52-week group, p21-positive cells, rather than GST-P-positive cells, were observed preferentially in the region consisting of histopathologically malignant cells. The present study demonstrated that during the process of tamoxifen-induced hepatocarcinogenesis, expression levels of the mRNA and protein of p21 were increased. The significance of the increased expression of p21 during hepatocarcinogenesis is discussed.
影响因子：
3.7
作者：
NODA, A;NING, Y;SMITH, JR
通讯作者：
SMITH, JR
DOI：
10.1093/jnci/90.18.1371
发表时间：
1998-09-16
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
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作者：
Fisher, B;Costantino, JP;Wolmark, N
通讯作者：
Wolmark, N