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甲状旁腺肿瘤中的p53/MDM2信号通路异常:p21(WAF-1)和MDM2在甲状旁腺腺瘤中常过度表达。

p53/MDM2 Pathway Aberrations in Parathyroid Tumors: p21(WAF-1) and MDM2 Are Frequently Overexpressed in Parathyroid Adenomas.

作者信息

Arribas Begona, Cristobal Eva, Alcazar Jose A., Tardio Juan, Matinez-Montero Juan C., Polo Jose R., Carrion Rafael, Gil Laura, Azanedo Marta, Rojas Jose M., Menarguez Javier

机构信息

MD, PHD.

出版信息

Endocr Pathol. 2000 Autumn;11(3):251-257. doi: 10.1385/ep:11:3:251.

Abstract

Parathyroid adenomas (PTAs) are the main cause of primary hyperparathyroidism. Cell cycle regulation in normal parathyroid tissue (NPT) and PTA remains largely unknown. We have systematically explored several components involved in the p53/MDM2/p19(ARF) pathway in PTA and compared the results were with NPT. Forty-six PTA and 12 NPT were immunostained with anti-p21(WAF-1), MDM2, p53, and p27(KP1) antibodies. The slides were processed by cytometry and the results were statistically analyzed using nonparametric methods (Mann-Whitney test). p2l(WAF-1) and MDM2 expression were significantly higher in PTA compared with NPT (p < 0.05). The opposite results were found for p27(KIP1) (p< 0.05). Occasional p53 staining was found in some PTA, albeit no significant difference was found in comparison with NPT. In conclusion, MDM2 and p2l(WAF-1) are the proteins more overexpressed in PTA. These findings are surprising taking into account the benign nature of PTA, making them suitable candidates for further molecular analysis.

摘要

甲状旁腺腺瘤(PTAs)是原发性甲状旁腺功能亢进的主要病因。正常甲状旁腺组织(NPT)和甲状旁腺腺瘤中的细胞周期调控在很大程度上仍不清楚。我们系统地研究了甲状旁腺腺瘤中p53/MDM2/p19(ARF)通路的几个组成部分,并将结果与正常甲状旁腺组织进行了比较。46例甲状旁腺腺瘤和12例正常甲状旁腺组织用抗p21(WAF-1)、MDM2、p53和p27(KP1)抗体进行免疫染色。玻片经流式细胞术处理,结果采用非参数方法(曼-惠特尼检验)进行统计学分析。与正常甲状旁腺组织相比,甲状旁腺腺瘤中p21(WAF-1)和MDM2的表达显著更高(p<0.05)。p27(KIP1)的结果则相反(p<0.05)。在一些甲状旁腺腺瘤中偶尔发现p53染色,尽管与正常甲状旁腺组织相比没有发现显著差异。总之,MDM2和p21(WAF-1)是在甲状旁腺腺瘤中过度表达较多的蛋白质。考虑到甲状旁腺腺瘤的良性性质,这些发现令人惊讶,使其成为进一步分子分析的合适候选对象。

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