Cromme F V, Snijders P J, van den Brule A J, Kenemans P, Meijer C J, Walboomers J M
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
Oncogene. 1993 Nov;8(11):2969-75.
Squamous cell carcinomas of the uterine cervix (n = 23) were selected for the presence of human papillomavirus type 16 (HPV 16) using the polymerase chain reaction (PCR). Localization of transcripts coding for the E7 protein was demonstrated in neoplastic cells with RNA in situ hybridization. Consecutive tissue sections were investigated for expression of the major histocompatibility complex class I (MHC-I) and c-myc using immunohistochemical double staining procedures, since a role has been suggested for the c-myc protein in MHC-I down-regulation and c-myc overexpression has been described in cervical carcinomas. Reduced expression of class I heavy chains was observed in neoplastic cells from 18 out of 23 carcinomas (78%). Varying levels of c-myc overexpression were observed in 12 carcinomas (52%), from which four showed positive MHC-I expression in c-myc overexpressing cells. In the remaining eight c-myc overexpressing carcinomas MHC-I down-regulation was observed. Additional RNA in situ hybridization with class I heavy chain locus-specific RNA-probes revealed presence of class I mRNAs in those neoplastic cells that show negative staining for MHC-I protein. These data strongly indicate that MHC-I down-regulation in cervical carcinomas involves post-transcriptional mechanisms, not directly related to E7 transcription and overexpression of c-myc.
采用聚合酶链反应(PCR),选取23例子宫颈鳞状细胞癌检测人乳头瘤病毒16型(HPV 16)的存在情况。利用RNA原位杂交技术在肿瘤细胞中证实了编码E7蛋白的转录本的定位。由于有研究提示c-myc蛋白在MHC-I下调中发挥作用,且在宫颈癌中已观察到c-myc过表达,因此采用免疫组织化学双重染色法对连续组织切片进行主要组织相容性复合体I类(MHC-I)和c-myc表达情况的研究。在23例癌组织中的18例(78%)肿瘤细胞中观察到I类重链表达降低。在12例癌组织(52%)中观察到不同程度的c-myc过表达,其中4例在c-myc过表达细胞中显示MHC-I阳性表达。在其余8例c-myc过表达的癌组织中观察到MHC-I下调。使用I类重链基因座特异性RNA探针进行的额外RNA原位杂交显示,在那些对MHC-I蛋白呈阴性染色的肿瘤细胞中存在I类mRNA。这些数据有力地表明,宫颈癌中MHC-I下调涉及转录后机制,与E7转录和c-myc过表达无直接关系。