Palefsky J M, Winkler B, Rabanus J P, Clark C, Chan S, Nizet V, Schoolnik G K
Department of Medicine, Howard Hughes Medical Institute, Stanford University, California 94305.
J Clin Invest. 1991 Jun;87(6):2132-41. doi: 10.1172/JCI115245.
The role of human papillomavirus (HPV) proteins in the pathogenesis of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer is poorly understood. To characterize E4 protein expression in 49 paraffin-embedded cervical biopsies representing different histopathologic grades of disease, antibodies were elicited to a synthetic peptide corresponding to amino acids 20-34 of a protein predicted to be encoded by the HPV 16 E4 open reading frame. The E4 protein was detected throughout the spectrum of CIN, from CIN1 to CIN3. Expression was localized to the cell nucleus, primarily in the superficial layers of the squamous cervical epithelium. Ultrastructural studies showed that the E4 protein was organized into compact, intranuclear arrays 25-35 nm in diameter. E4 protein expression was also demonstrated in some histologically normal tissues containing HPV 16 DNA, but not in any of five cervical cancers containing HPV 16 DNA. These results suggest that E4 protein expression may precede development of light microscopic tissue abnormalities, that it may continue through the spectrum of CIN, and that expression of this protein may be reduced or terminated in invasive cancer. The function of this protein remains unknown, but its nuclear localization may be consistent with a role in viral maturation.
人乳头瘤病毒（HPV）蛋白在宫颈上皮内瘤变（CIN）和浸润性宫颈癌发病机制中的作用尚不清楚。为了描述49例代表不同组织病理学分级疾病的石蜡包埋宫颈活检组织中E4蛋白的表达情况，制备了针对一种合成肽的抗体，该合成肽对应于预测由HPV 16 E4开放阅读框编码的蛋白的第20 - 34位氨基酸。在整个CIN范围内，从CIN1到CIN3都检测到了E4蛋白。其表达定位于细胞核，主要在宫颈鳞状上皮的表层。超微结构研究表明，E4蛋白组装成直径为25 - 35 nm的紧密核内阵列。在一些含有HPV 16 DNA的组织学正常组织中也证实了E4蛋白的表达，但在五个含有HPV 16 DNA的宫颈癌组织中均未检测到。这些结果表明，E4蛋白表达可能在光镜下组织异常出现之前就已发生，可能贯穿整个CIN范围，并且该蛋白的表达在浸润性癌中可能会降低或终止。该蛋白的功能尚不清楚，但其核定位可能与病毒成熟过程中的作用一致。
