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人乳头瘤病毒(HPV)诱导的肿瘤形成及宫颈癌中细胞RNA结合蛋白表达增加。

Increased expression of cellular RNA-binding proteins in HPV-induced neoplasia and cervical cancer.

作者信息

Fay Joanna, Kelehan Peter, Lambkin Helen, Schwartz Stefan

机构信息

School of Biological Sciences, Dublin Institute of Technology, Dublin, Ireland.

出版信息

J Med Virol. 2009 May;81(5):897-907. doi: 10.1002/jmv.21406.

Abstract

The expression profile of a panel of RNA-binding proteins (heterogeneous ribonucleoprotein (hnRNP) A1, hnRNP C1/C2, hnRNP H, hnRNP I, ASF/SF2, SR proteins, HuR and U2AF(65)) and markers of differentiation, proliferation and neoplasia (cytokeratin (CK) 13, CK-14, proliferating cell nuclear antigen (PCNA), Syndecan-1 and p16INK4a) were analyzed in 50 formalin fixed paraffin embedded cervical tissues using immunohistochemistry. The samples included histologically normal cervical epithelium, human papillomavirus (HPV) induced low-grade and high-grade pre-malignant lesions and cervical cancers. All samples were tested for HPV DNA using nested PCR. Forty-nine of the 50 tissue samples tested positive for HPV, 27 tissue samples (54%) were HPV-16 positive and 4 samples (8%) were HPV-18 positive. The immunohistochemistry results detected different expression levels of the various proteins in basal epithelial cells in histologically normal epithelium followed by an increase in expression in the intermediate layers, whereas the superficial layers remained negative for all tested RNA-binding proteins. Expression of all RNA-binding proteins increased in neoplastic lesions and highest expression was detected in cervical cancers. p16INK4a had a stronger association with high-grade lesions when compared with the RNA-binding proteins. The expression profile of the RNA-binding proteins is similar to PCNA expression in histologically normal epithelium as well as in lesions (low-grade and high-grade) and cervical cancers. As PCNA expression has been suggested to mimic HPV E6/E7 expression in cervical epithelium, the results suggest the RNA-binding protein analyzed here regulate HPV early gene expression directly and late gene expression indirectly.

摘要

采用免疫组织化学方法,对50例福尔马林固定石蜡包埋的宫颈组织中一组RNA结合蛋白(异质性核糖核蛋白(hnRNP)A1、hnRNP C1/C2、hnRNP H、hnRNP I、ASF/SF2、SR蛋白、HuR和U2AF(65))以及分化、增殖和肿瘤形成标志物(细胞角蛋白(CK)13、CK-14、增殖细胞核抗原(PCNA)、Syndecan-1和p16INK4a)的表达谱进行了分析。样本包括组织学正常的宫颈上皮、人乳头瘤病毒(HPV)诱导的低级别和高级别癌前病变以及宫颈癌。所有样本均采用巢式PCR检测HPV DNA。50个组织样本中有49个HPV检测呈阳性,27个组织样本(54%)为HPV-16阳性,4个样本(8%)为HPV-18阳性。免疫组织化学结果显示,在组织学正常上皮的基底上皮细胞中,各种蛋白质的表达水平不同,随后中间层表达增加,而所有检测的RNA结合蛋白在表层均为阴性。所有RNA结合蛋白在肿瘤性病变中的表达均增加,在宫颈癌中检测到最高表达。与RNA结合蛋白相比,p16INK4a与高级别病变的相关性更强。在组织学正常上皮以及病变(低级别和高级别)和宫颈癌中,RNA结合蛋白的表达谱与PCNA表达相似。由于有人提出PCNA表达可模拟宫颈上皮中HPV E6/E7的表达,因此结果表明,此处分析的RNA结合蛋白直接调节HPV早期基因表达,间接调节晚期基因表达。

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