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p63的表达与鼻咽癌的不同分期及EB病毒感染相关。

The expression of p63 is associated with the differential stage in nasopharyngeal carcinoma and EBV infection.

作者信息

Guo Can, Pan Zhi-Gang, Li Da-Jiang, Yun Jing-Ping, Zheng Mei-Zhen, Hu Zhe-Yu, Cheng Li-Zhen, Zeng Yi-Xin

机构信息

State Key Laboratory of Oncology in Southern China.

出版信息

J Transl Med. 2006 May 29;4:23. doi: 10.1186/1479-5876-4-23.

Abstract

BACKGROUND

Nasopharyngeal carcinoma (NPC) is common among Southern Chinese and the main histology is the undifferentiated carcinoma associated with Epstein-Barr virus (EBV) infection. p63 is a recently proved member of the p53 family based on the structural similarity to p53, but its function in NPC is still unknown. This study was aimed to investigate the association between p63 and NPC.

RESULTS

p63 was expressed in 100% (202/202) of nasopharyngeal carcinoma (NPC) tissues but not in 29 nasopharynx inflammation and 17 non-cancerous nasopharyngeal epidermises on a tissue microarray by immunohistostaining. Further investigation suggested that the p63 expression was associated with the differential stage of NPC: p63 strong staining in Keratinizing squamous cell carcinoma, differentiated non-keratinizing NPC and undifferentiated non-keratinizing NPC presented the percentage of 5/8 (62.5%), 43/48 (92.5%) and 50/50 (100%), respectively. A significant difference (p = 0.001) existed between the keratinizing and non-keratinizing groups. No pathogenic mutations were detected in p63 gene in 12 primary NPC tissues and matched peripheral blood lymphocytes (PBL). Half-life measurement study revealed distinct stability of p63 protein in the different cell lines, especially between the carcinoma cell lines with EBV infection and the non-cancerous cell lines. The results of immunoprecipitation suggested a direct interaction between Epstein-Barr virus nuclear antigen 5 (EBNA-5) and p63 protein in NPC, and this binding would increase the stability of p63.

CONCLUSION

Our data suggested p63 might be used as an adjunct diagnostic marker of NPC and contributed a new way to understand the contribution of the EBV in the pathogenesis of NPC.

摘要

背景

鼻咽癌(NPC)在中国南方人群中较为常见,主要组织学类型为与爱泼斯坦-巴尔病毒(EBV)感染相关的未分化癌。p63是最近基于与p53的结构相似性而被证实的p53家族成员,但其在鼻咽癌中的功能仍不清楚。本研究旨在探讨p63与鼻咽癌之间的关联。

结果

通过免疫组织化学染色,在组织芯片上,p63在100%(202/202)的鼻咽癌(NPC)组织中表达,但在29例鼻咽部炎症组织和17例非癌性鼻咽表皮组织中未表达。进一步研究表明,p63表达与鼻咽癌的不同分期相关:在角化性鳞状细胞癌、分化型非角化性鼻咽癌和未分化型非角化性鼻咽癌中,p63强染色的比例分别为5/8(62.5%)、43/48(92.5%)和50/50(100%)。角化性和非角化性组之间存在显著差异(p = 0.001)。在12例原发性鼻咽癌组织及配对的外周血淋巴细胞(PBL)中未检测到p63基因的致病突变。半衰期测量研究显示p63蛋白在不同细胞系中的稳定性不同,尤其是在EBV感染的癌细胞系和非癌性细胞系之间。免疫沉淀结果表明,在鼻咽癌中,爱泼斯坦-巴尔病毒核抗原5(EBNA-5)与p63蛋白直接相互作用,这种结合会增加p63的稳定性。

结论

我们的数据表明p63可能作为鼻咽癌的辅助诊断标志物,并为理解EBV在鼻咽癌发病机制中的作用提供了新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6486/1525203/2625031966e8/1479-5876-4-23-1.jpg

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