Abstract
Particular types of human papillomavirus (HPV) are associated with skin cancer of epidermodysplasia verruciformis (EV) patients. Here, we show, for the first time, that the E7 gene of EV-associated HPV8 possesses a potential oncogenic transforming ability. The HPV8 E7 open reading frame (ORF) and the HPV16 E7 ORF were cloned under the SV40 promoter/enhancer to construct recombinant plasmids pcD2-8E7 and pcD2-16E7, respectively. Transfection of primary rat embryonal fibroblasts having an activated H-ras gene revealed that pcD2-8E7 as well as pcD2-16E7 induced transformation of cells in G418-resistant colonies at an efficiency of 12.3% and 42.9%, respectively. The resulting transformed cell lines induced by pcD2-8E7 and activated H-ras were tumorigenic when injected into syngeneic immunocompetent rats. The potential tumorigenicity of HPV8 E7 seemed to be higher than that of HPV16 E7.
MeSH Terms
Animals
Cell Line, Transformed
Cell Transformation, Neoplastic/genetics
Cell Transformation, Viral/genetics
Fibroblasts/physiology
Gene Expression Regulation, Neoplastic/genetics
Gene Expression Regulation, Viral/genetics
Genes, Viral/genetics
Genes, ras/genetics
Humans
Neoplasm Transplantation
Open Reading Frames/genetics
Papillomaviridae/genetics
Plasmids/genetics
Rats
Rats, Inbred F344
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Nishikawa T
Department of Molecular Biology, Sapporo Medical College.
Yamashita T
Yamada T
Kobayashi H
Ohkawara A
Fujinaga K
References (25)
25 references, click to expand
-
DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells.
Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373-6
PMID: 286319
-
Simultaneous detection and typing of genital human papillomavirus DNA using the polymerase chain reaction.
J Gen Virol. 1991 May;72 ( Pt 5):1039-44
PMID: 1851805
-
Epidermodysplasia verruciformis: a model for understanding the oncogenicity of human papillomaviruses.
Ciba Found Symp. 1986;120:157-74
PMID: 3013521
-
The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1A.
Cell. 1988 May 20;53(4):539-47
PMID: 2836062
-
Human papillomavirus type 16 DNA sequence.
Virology. 1985 Aug;145(1):181-5
PMID: 2990099
-
Human papillomavirus type 16 cooperates with activated ras and fos oncogenes in the hormone-dependent transformation of primary mouse cells.
Proc Natl Acad Sci U S A. 1988 Dec;85(23):8820-4
PMID: 2848240
-
The primary structure of major viral RNA in a rat cell line transfected with type 47 human papillomavirus DNA and the transforming activity of its cDNA and E6 gene.
Virology. 1989 Dec;173(2):551-65
PMID: 2556842
-
Cellular transformation by human papillomavirus DNA in vitro.
Science. 1984 Aug 10;225(4662):634-6
PMID: 6330900
-
The E7 protein of human papillomavirus 8 is a nonphosphorylated protein of 17 kDa and can be generated by two different mechanisms.
Virology. 1990 Nov;179(1):428-36
PMID: 2171214
-
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
Anal Biochem. 1983 Jul 1;132(1):6-13
PMID: 6312838
-
Characterization of a human papillomavirus from epidermodysplasia verruciformis lesions of a patient from Upper-volta.
Int J Cancer. 1981 May 15;27(5):645-50
PMID: 6270020
-
A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer.
EMBO J. 1984 May;3(5):1151-7
PMID: 6329740
-
A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions.
Proc Natl Acad Sci U S A. 1983 Jun;80(12):3812-5
PMID: 6304740
-
Detection of specific sequences among DNA fragments separated by gel electrophoresis.
J Mol Biol. 1975 Nov 5;98(3):503-17
PMID: 1195397
-
Epidermodysplasia verruciformis-associated human papillomavirus 8: genomic sequence and comparative analysis.
J Virol. 1986 May;58(2):626-34
PMID: 3009874
-
Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product.
EMBO J. 1989 Dec 20;8(13):4099-105
PMID: 2556261
-
Cellular targets for transformation by the adenovirus E1A proteins.
Cell. 1989 Jan 13;56(1):67-75
PMID: 2521301
-
High-efficiency transformation of mammalian cells by plasmid DNA.
Mol Cell Biol. 1987 Aug;7(8):2745-52
PMID: 3670292
-
A novel type of human papilloma virus DNA from the lesion of epidermodysplasia verruciformis.
Jpn J Cancer Res. 1986 Oct;77(10):978-84
PMID: 3023264
-
Human papillomavirus type 5 and skin cancer in renal allograft recipients.
Lancet. 1987 Jul 18;2(8551):151-2
PMID: 2885608
-
The physical state of human papillomavirus 16 DNA in cervical carcinoma and cervical intraepithelial neoplasia.
Cancer. 1990 Nov 15;66(10):2155-61
PMID: 2171746
-
Comparison of the in vitro transforming activities of human papillomavirus types.
EMBO J. 1988 Jun;7(6):1815-20
PMID: 2458921
-
Transformation of human fibroblasts and keratinocytes with human papillomavirus type 16 DNA.
J Virol. 1987 Apr;61(4):1061-6
PMID: 2434663
-
Involvement of human papillomavirus type 8 genes E6 and E7 in transformation and replication.
J Virol. 1988 Oct;62(10):3655-61
PMID: 2843666
-
SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene.
Cell. 1988 Jul 15;54(2):275-83
PMID: 2839300