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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Tumorigenic transformation of primary rat embryonal fibroblasts by human papillomavirus type 8 E7 gene in collaboration with the activated H-ras gene. 166 18

Skin cancers induced in mice by UV radiation often exhibit a regressor phenotype. In order to determine how tumors escape the immune defenses of the normal immunocompetent host, we sought to isolate progressor variants from a UV radiation-induced C3H mouse regressor fibrosarcoma cell line, UV-2240, by transfection with an activated Ha-ras oncogene. A cotransfection protocol using pSV2-neo DNA, which confers resistance to the antibiotic G418, was used to select transfected cells. Injection of Ha-ras-transfected UV-2240 cells s.c. into immunocompetent C3H mice produced tumors in four of 36 animals. In contrast, UV-2240 cells transfected with pSV2-neo DNA alone or mock transfected with CaPO4 did not produce tumors in normal C3H mice. DNAs from cell lines established from Ha-ras-induced tumors contained unique Ha-ras sequences in addition to those sequences endogenous to UV-2240 cells. However, the Ha-ras-induced progressor variants did not overexpress the Mr 21,000 protein. The Ha-ra-induced progressor variants produced experimental lung metastasis in both normal C3H and nude mice, although they induced more lung nodules in nude mice than in normal C3H mice. In addition, all four Ha-ras-induced progressor variants produced significantly more experimental lung metastases in nude mice than did the parent UV-2240 cell line. However, both the parental UV-2240 cell line and the Ha-ras-induced progressor variants expressed similar levels of H-2Kk and H-2Dk antigens and were immunologically cross-reactive, as determined by in vitro cytotoxic T-lymphocyte and in vivo immunization-challenge assays. These results indicate that the progressor phenotype of the Ha-ras-induced tumor variants is not due to loss of tumor-specific transplantation or Class I major histocompatibility complex antigens. This implies that some tumor cells can escape the immune defenses of the normal immunocompetent host by mechanisms other than loss of tumor-specific transplantation and Class I major histocompatibility antigens.
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PMID:Immune response to progressor variants derived from transfection of an ultraviolet radiation-induced C3H mouse regressor tumor cell line with activated Harvey-ras oncogene. 218 82

High-molecular-weight DNA isolated from eight fresh human skin cancers occurring on sun-exposed body sites were assayed for their ability to transform NIH 3T3 cells. A cotransfection protocol using pSV2-neo DNA, which confers resistance to the antibiotic G418, was used to select cells that had taken up the transfected DNA. About 2 weeks after transfection, G418-resistant colonies were pooled and injected s.c. into athymic nude mice. The NIH 3T3 cells transfected with DNA from six of the human skin cancers induced tumors in nude mice. DNAs from all six tumor cell lines contained human alu sequences. Southern blot hybridization with ras-specific probes revealed that DNAs from the four alu-rich tumors contained the human Ha-ras oncogene, in addition to that of the NIH 3T3 controls. In contrast, DNAs from the other two tumors did not contain any of the known oncogenes tested, except those endogenous to NIH 3T3 cells. DNAs from three of four first cycle tumorigenic transformants gave rise to morphologically transformed foci when assayed in a second cycle of transfection. DNAs from all three secondary transformants contained discrete human alu sequences, and in addition, contained Ha-ras sequences similar to those present in their respective primary transformants. Interestingly, DNA from both primary and secondary transformants of one particular human squamous cell carcinoma contained highly amplified copies of the Ha-ras oncogene. These results suggest that activation of the Ha-ras oncogene may be common in human skin cancers originating on sun-exposed body sites. Further characterization of the Ha-ras oncogenes present in these human skin cancers may provide information on the molecular mechanisms by which UV radiation of the sun induces human neoplasms on exposed body sites.
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PMID:Detection and identification of activated oncogenes in human skin cancers occurring on sun-exposed body sites. 337 Jun 35

Ultraviolet radiation-induced murine skin cancers often express highly immunogenic tumor-specific transplantation antigens (TSTA). The relationship between expression of TSTA and neoplastic transformation is not clear. I have used DNA transfection techniques to determine whether expression of TSTA and the transformed phenotype are associated at the genetic level. C3H mouse embryo fibroblast 10T1/2 clone 8 cells were transfected with high-molecular-weight genomic DNA from a highly antigenic ultraviolet radiation-induced 2240 tumor cell line. A cotransfection protocol using pSV2-neo DNA, which confers resistance to the antibiotic G418, was used to select cells that had taken up foreign DNA. Morphologically transformed, G418-resistant colonies were isolated and tested for expression of 2240 tumor-specific antigens by means of a cytotoxic T-lymphocyte assay. None of the 12 morphologically transformed colonies tested expressed 2240 tumor-specific antigens on their cell surface as revealed by their inability to be killed by 2240 tumor-specific cytotoxic T-lymphocytes. In addition, the morphologically transformed cells did not inhibit the killing of 51Cr-labeled 2240 cells by 2240 tumor-specific cytotoxic T-lymphocytes in a cold-target inhibition assay. Cell surface expression of Class I major histocompatibility antigens was not significantly altered in 2240 DNA transformants. These results demonstrate that, in ultraviolet radiation-induced murine skin tumors, there is not coordinate expression of TSTA and the transformed phenotype, even though most ultraviolet radiation-induced skin tumors exhibit both characteristics. This finding suggests that the two phenotypes are controlled by separate genes.
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PMID:Relationship between expression of tumor-specific transplantation antigens and neoplastic transformation in an ultraviolet radiation-induced murine skin cancer. 377 49

Human papillomavirus (HPV) 5 and HPV8 are often detected in skin cancers developed in patients suffering from epidermodysplasia verruciformis, as well as in skin cancers developed in immunosuppressed patients. In the present study, in order to examine the transforming activity of the HPV8E7 gene, the HPV8E7 and HPV8E6/E7 genes were cloned into the expression vector (pcD2-Y), under the SV40 enhancer/promoter to construct pcD2-8E7 and pcD2-8E6/E7, respectively. The E7 and E6/E7 genes of genital high-risk HPV16 were also cloned into pcD2-Y to construct pcD2-16E7 and pcD2-16E6/E7, respectively. They were tested for their ability to collaboratively transform primary rat embryo fibroblasts (REFs) with activated H-ras gene. Transfection experiments of REFs having an activated H-ras gene revealed that pcD2-8E7, as well as pcD2-16E7 and pcD2-16E6/E7, induced transformation of cells in G418-resistant colonies at efficiencies of 11.9%, 43.0% and 53.0%, respectively. Transformed cell lines induced by activated H-ras gene and pcD2-8E7 or pcD2-16E7 were named 8RE and 16RE cell lines, respectively. Tumor induction in syngeneic newborn rats by injected the 8RE cells was higher than that of the 16RE cells. In cytological and histological examination, the 8RE cell lines and their induced tumors were different from the 16RE cell lines and their induced tumors. The 8RE cell lines showed the characteristic transformation with efficient growth ability on plastic and colony formation in 0.3% soft agar. These results support the hypothesis that the HPV8E7 gene plays an important role in the carcinogenesis of skin cancers.
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PMID:[Experimental study on carcinogenesis by human papillomavirus type 8 E7 gene]. 792 81

Due to their limited life time in culture and their relative resistance to DNA transfection, primary fibroblasts derived from UV-hypersensitive patients could not be used for cloning DNA repair gene and studying stable complementation with wild-type DNA repair genes. Primary cells were only used for complementation analysis after transient expression through cell fusion. DNA microinjection and transfection. We report the retroviral-mediated highly efficient transfer and stable expression of XPD/ERCC2 gene in fibroblast strains from eight different patients using the LXPDSN retroviral vector. Cells derived from skin biopsies of xeroderma pigmentosum and trichothiodystrophy patients were incubated with vector-containing suspension and selected with the neomycin-analog G418. LXPDSN vector specifically complemented cells belonging to the XP-D group. Long-term reversion of repair-deficient phenotype, monitored by UV survival and UDS analysis, has been achieved in these diploid fibroblasts. We demonstrate this methodology is a powerful tool to study phenotypic reversion of nucleotide excision repair-deficient cells such as cellular DNA repair properties and we suggest that it may be used to study other cellular parameters (cell cycle regulation, p53 stability or immunosurveillance-controlling factors) involved in UV-induced skin cancers and which reliability requires the use of untransformed cells.
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PMID:Long-term complementation of DNA repair deficient human primary fibroblasts by retroviral transduction of the XPD gene. 896 Jan 28