title: Tumorigenicity of the E6 and E6-E7 gene constructions derived from human papillomavirus type 33.
abstract: Human papillomavirus type 33 (HPV33) belongs to the group of HPV types frequently found in severe cervical dysplasias and carcinomas. By analogy with HPV types 16 and 18 selectively expressing E6 and E7 genes in malignant tissues, we studied the HPV33 E6 and E7 open reading frames in various configurations with upstream promoter and noncoding region (NCR) known to contain a particular 78-bp tandem repeat. HPV DNA fragments were cloned into expression vectors between the SV40 or the mouse metallothionein I promoter and the neo gene, transfected into NIH3T3 cells, selected by neo resistance, and inoculated into nude mice. In these bioassays, a weak transforming activity was detected for E6 open reading frame, and could be significantly enhanced either by the NCR or the E7 open reading frame. No tumorigenicity could be detected for E7 alone or in configuration with the upstream NCR. Further analyses of tumor cells showed that HPV33-derived genes were not sufficient to induce an anchorage-independent phenotype and, interstingly, there was no requirement for virus-transfected tumor cells to retain HPV sequences during tumor progression. We concluded that the transformation function of HPV33 resides in E6 gene as assayed by tumorigenicity. An enhancer of the E6 promoter is located in the NCR. On the other hand, in the absence of the NCR, E6 tumorigenicity may be augmented by the E7.
authors.affiliation: Laboratory of Cellular and Molecular Biology, C.N.R.S., Institute of Cancer and Immunogenetics, Villejuif, France.
authors.forename: H
authors.initials: H
authors.lastname: Kitasato
authors.forename: J
authors.initials: J
authors.lastname: Hillova
authors.forename: M
authors.initials: M
authors.lastname: Lenormand
authors.forename: M
authors.initials: M
authors.lastname: Hill
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005814:Genes, Viral; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000209:etiology*; D027383:Papillomaviridae / Q000235:genetics*; D014162:Transfection
chemical_list: D004279:DNA, Viral