Absence of nuclear p16 from Epstein-Barr virus-associated undifferentiated nasopharyngeal carcinomas
Absence of nuclear p16 from Epstein-Barr virus-associated undifferentiated nasopharyngeal carcinomas
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DOI：
10.1097/00005537-200001000-00017
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发表时间：
2000-01-01
期刊：
影响因子：
2.6
通讯作者：
Takakuwa, T
中科院分区：
文献类型：
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作者：
Shibosawa, E;Tsutsumi, K;Takakuwa, T
目的：在大多数未分化鼻咽癌(UNPC，世界卫生组织III型)中检测到EB病毒(EBV)。然而，EBV相关的UNPC致癌的确切机制仍有待阐明。一个重要的悬而未决的问题是：在EBV相关的非PC发育过程中，正常的细胞周期是如何被解除调控的？P16(CDKN2)基因编码一种核蛋白p16，它抑制D型细胞周期蛋白/细胞周期蛋白依赖的蛋白复合体对视网膜母细胞瘤基因产物(PRB)的磷酸化，从而阻断G(1)细胞周期进程，本研究的目的是确定p16缺失是否与EBV相关UNPC的发生有关。方法：我们用免疫组织化学方法检测28例患者UNPC中的p16和pRB，并用原位杂交检测EBV编码的小RNA(EBER)。结果：28例UNPC中有23例(82.1%)未检测到p16。PRb表达阳性，EBER阳性22例(78.6%)。PIE的缺失与EBER在UNPC中的存在有关(P<；.0001)：22个EBER+UNPC中没有一个表达p16，而6个EBER-UNPC中有5个表达，结论：我们的数据表明，PIE相关的细胞周期调控的丧失在EBV相关UNPC的发展中起着重要作用。
Objective: Epstein-Barr virus (EBV) is detected in the majority of undifferentiated nasopharyngeal carcinomas (UNPCs, World Health Organization type III). However, the exact mechanism involved in the carcinogenesis of EBV-associated UNPCs remains to be elucidated. An important unresolved question is: how is the normal cell cycle deregulated during EBV-associated UNPC development? The p16(CDKN2) gene encodes a nuclear protein, p16, which inhibits the D-type cyclin/cyclin-dependent kinase complexes that phosphorylate the retinoblastoma gene product (pRb), thus blocking G(1) cell cycle progression, The objective of this study was to determine whether p16 absence is involved in the development of EBV-associated UNPCs, Methods: We performed immunohistochemistry to detect p16 and pRb and in situ hybridization to detect EBV-encoded small RNA (EBER) in UNPCs from 28 patients, Results: No p16 was detected in 23 of 28 UNPCs (82.1%), whereas pRb was expressed in all those examined and EBER was detected in 22 of 28 (78.6%). The absence of pie was associated with the presence of EBER in UNPCs (P < .0001): none of the 22 EBER+ UNPCs expressed p16, whereas 5 of 6 EBER- UNPCs did, Conclusion: Our data suggest that loss of pie-related cell cycle regulation plays an important role in the development of EBV-associated UNPCs.