Takami Y, Kondoh G, Saito J, Noda K, Sudiro T M, Sjahrurachman A, Warsa U C, Yutsudo M, Hakura A
Department of Tumor Virology, Osaka University, Suita, Japan.
Int J Cancer. 1991 Jun 19;48(4):516-22. doi: 10.1002/ijc.2910480407.
Human papillomavirus (HPV) type 52 from a cervical carcinoma in Indonesia was molecularly cloned and characterized. By hybridization with cervical carcinoma DNAs from Indonesian patients, HPV 52 was detected in 3 of 52 cases (6%), whereas HPV 16 and 18 were detected in 8 and 7 cases, respectively (15% and 13%). Sequence analysis revealed that the E6-E7 ORFs contained several DNA binding motifs (Cys-X-X-Cys) like previously sequenced HPVs. The E6 ORF also contained splice donor and acceptor signals, which may allow the expression of E6* protein. The E7 ORF encoded an amino acid sequence that is conserved in some DNA tumor viruses and is involved in binding to Rb protein and in cellular transformation. Transfection of a subgenomic fragment of HPV 52 under the control of a heterologous promoter showed that the E7 ORF alone induced anchorage-independent growth of established rodent cells and immortalized primary rat embryo fibroblasts (REF), and that in cooperation with activated ras, it induced malignant transformation of REF. The E6 ORF also induced, less efficiently, anchorage-independent growth. These results strongly suggest that HPV 52, like HPV 16 and 18, has oncogenic potential.
对来自印度尼西亚一名宫颈癌患者的52型人乳头瘤病毒(HPV)进行了分子克隆和特性分析。通过与印度尼西亚患者的宫颈癌DNA杂交,在52例病例中的3例(6%)检测到HPV 52,而分别在8例和7例病例中检测到HPV 16和18(15%和13%)。序列分析显示,E6-E7开放阅读框(ORF)含有几个DNA结合基序(半胱氨酸- X - X -半胱氨酸),类似于先前测序的HPV。E6 ORF还含有剪接供体和受体信号,这可能允许E6*蛋白的表达。E7 ORF编码的氨基酸序列在一些DNA肿瘤病毒中保守,参与与Rb蛋白的结合和细胞转化。在异源启动子控制下转染HPV 52的亚基因组片段表明,单独的E7 ORF可诱导已建立的啮齿动物细胞锚定非依赖性生长,并使原代大鼠胚胎成纤维细胞(REF)永生化,并且与激活的ras协同作用时,可诱导REF发生恶性转化。E6 ORF也能诱导锚定非依赖性生长,但其效率较低。这些结果强烈表明,HPV 52与HPV 16和18一样,具有致癌潜力。