Sun Q, Tsutsumi K, Yokoyama M, Pater M M, Pater A
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Int J Cancer. 1993 Jun 19;54(4):656-62. doi: 10.1002/ijc.2910540422.
The association between human papillomavirus (HPV) type 16 and cervical squamous-cell carcinoma has been well documented, and HPV 16 DNA has been shown to immortalize human genital keratinocytes in vitro. Using a panel of cytokeratin(CK)-specific antibodies, we examined the CK expression pattern, an important characteristic of epithelia, of the stratified squamous epithelium reconstructed in vivo from monolayer cultures of 2 human ectocervical and 3 human foreskin keratinocyte cell lines immortalized by HPV 16 DNA. Whereas the abnormal epithelium formed from these grafts presented certain aspects of mature terminal differentiation, such as morphology and expression of CK10/11, the expression patterns for CK19, and especially CK13, were more obviously abnormal. CK18 expression was not detectable in any of the epithelia formed from the 5 cell lines. In contrast, for an HPV-16-immortalized endocervical cell line and the CaSki cervical-carcinoma cell line there was expression of CK18. Our results indicate that HPV-16-induced immortalization of keratinocytes is associated with disruption of the normal CK expression pattern in stratified squamous epithelium and that expression of particular CKs can be differentially disrupted.
人乳头瘤病毒16型(HPV-16)与宫颈鳞状细胞癌之间的关联已有充分记录,并且HPV-16 DNA已被证明可在体外使人泌尿生殖角质形成细胞永生化。我们使用一组细胞角蛋白(CK)特异性抗体,检测了由HPV-16 DNA永生化的2种人宫颈外膜和3种人包皮角质形成细胞系的单层培养物在体内重建的复层鳞状上皮的CK表达模式,这是上皮细胞的一个重要特征。虽然由这些移植物形成的异常上皮呈现出某些成熟终末分化的特征,如形态和CK10/11的表达,但CK19,尤其是CK13的表达模式更明显异常。在由这5种细胞系形成的任何上皮中均未检测到CK18的表达。相比之下,对于一个HPV-16永生化的宫颈内膜细胞系和CaSki宫颈癌细胞系,存在CK18的表达。我们的结果表明,HPV-16诱导的角质形成细胞永生化与复层鳞状上皮中正常CK表达模式的破坏有关,并且特定CK的表达可被差异性破坏。