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评估 HPV16 E7 表达在头颈部癌的细胞系和临床标本中的作用。

Evaluation of HPV16 E7 expression in head and neck carcinoma cell lines and clinical specimens.

机构信息

Division of Gene Therapy Science, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.

Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.

出版信息

Sci Rep. 2020 Dec 17;10(1):22138. doi: 10.1038/s41598-020-78345-8.

Abstract

Human papillomavirus (HPV) 16 infection in the oropharynx is one of the major risk factors for oropharyngeal carcinoma. Although the HPV E6 and E7 proteins are known to have a role in head and neck carcinogenesis, whether their expression is maintained once the tumour has developed still remains unclear. We evaluated the expression of these proteins in HPV16-positive cancer cell lines and clinical oropharyngeal specimens. Two out of the four commercially available antibodies directed against the E7 protein could detect the E7 protein overexpressed in the 293FT cells, human embryonic kidney cells, although none of the four commercially available anti-E6 antibodies could detect the overexpressed E6 protein. Whereas HPV16-positive head and neck or cervical carcinoma cell lines expressed the E7 mRNA, the antibodies with an ability to detect the E7 protein could not detect it in western blotting in these HPV16-positive cell lines. In clinical specimens, E7 protein was partially detected in p16-positive area in p16-positive and HPV16 DNA-positive samples, but not in p16-negative and HPV DNA-negative or p16-positive and HPV DNA-negative samples. Consistent with these findings, the E7 protein was poorly translated from the endogenous structure of the E7 mRNA, although significant E7 mRNA expression was detected in these samples. Our findings indicate that E7 protein is partially expressed in p16-positive area in p16-positive and HPV16 DNA-positive clinical specimens.

摘要

人乳头瘤病毒(HPV)16 感染口咽是口咽癌的主要危险因素之一。虽然 HPV E6 和 E7 蛋白被认为在头颈部肿瘤发生中起作用,但肿瘤发展后它们的表达是否仍然存在尚不清楚。我们评估了这些蛋白在 HPV16 阳性癌细胞系和临床口咽标本中的表达。四种市售的针对 E7 蛋白的抗体中的两种可以检测到 293FT 细胞中过表达的 E7 蛋白,293FT 细胞是人胚肾细胞,尽管四种市售的抗 E6 抗体均不能检测到过表达的 E6 蛋白。虽然 HPV16 阳性的头颈部或宫颈癌细胞系表达 E7 mRNA,但能够检测到 E7 蛋白的抗体在这些 HPV16 阳性细胞系中的 Western blot 中无法检测到它。在临床标本中,E7 蛋白在 p16 阳性且 HPV16 DNA 阳性的样本中 p16 阳性区域部分被检测到,但在 p16 阴性且 HPV DNA 阴性或 p16 阳性且 HPV DNA 阴性的样本中未被检测到。与这些发现一致的是,尽管在这些样本中检测到显著的 E7 mRNA 表达,但 E7 蛋白从 E7 mRNA 的内源性结构中翻译较差。我们的研究结果表明,E7 蛋白在 p16 阳性且 HPV16 DNA 阳性的临床标本中 p16 阳性区域部分表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9697/7747560/f97b73432591/41598_2020_78345_Fig1_HTML.jpg

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