Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Mar;83(6):1738–1742. doi: 10.1073/pnas.83.6.1738

DNA amplification and neoplastic transformation mediated by a herpes simplex DNA fragment containing cell-related sequences.

R J Jariwalla, B Tanczos, C Jones, J Ortiz, S Salimi-Lopez
PMCID: PMC323159  PMID: 3006067

Abstract

The transforming potential of the herpes simplex virus type 2 (HSV-2) BamHI fragment E (map position 0.533-0.583) encoding the 140-kDa ribonucleotide reductase was assayed by transfection in established Rat-2 cells. Foci of refractile, morphologically distinguishable cells were induced at lower efficiency and after a longer incubation period as compared to the human tumor oncogene EJ-Ha-ras. Focus-derived BamHI fragment E-transformed cell lines formed medium-to-large (0.1-0.25 mm) colonies in soft agar and were tumorigenic in immunocompetent syngeneic rats. Southern blot analysis of normal rat DNA after EcoRI digestion revealed specific DNA segments homologous to HSV-2 BamHI fragment-E DNA. In BamHI fragment E-transformed and tumor-derived lines, about 8- to 30-fold amplification was detected in a subset of the specific HSV-related DNA segments. In addition, extrachromosomal DNA was isolated from transformed cells by plasmid rescue and contained the left-hand 70% of HSV-2 Bam HI fragment E fused to rat DNA. These results indicate the presence in normal cells of nonrepetitive DNA segments, related to the transforming HSV-2 fragment, that can be targeted for genetic alterations associated with neoplastic transformation.

Full text

PDF
1739

Images in this article

1740Image
on p.1740
1740Image
on p.1740
1740Image
on p.1740
1740Image
on p.1740
1741Image
on p.1741
1741Image
on p.1741
1741Image
on p.1741
1741Image
on p.1741

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson K. P., Frink R. J., Devi G. B., Gaylord B. H., Costa R. H., Wagner E. K. Detailed characterization of the mRNA mapping in the HindIII fragment K region of the herpes simplex virus type 1 genome. J Virol. 1981 Mar;37(3):1011–1027. doi: 10.1128/jvi.37.3.1011-1027.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bacchetti S., Evelegh M. J., Muirhead B., Sartori C. S., Huszar D. Immunological characterization of herpes simplex virus type 1 and 2 polypeptide(s) involved in viral ribonucleotide reductase activity. J Virol. 1984 Feb;49(2):591–593. doi: 10.1128/jvi.49.2.591-593.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Camacho A., Spear G. Transformation of hamster embryo fibroblasts by a specific fragment of the herpes simplex virus genome. Cell. 1978 Nov;15(3):993–1002. doi: 10.1016/0092-8674(78)90283-0. [DOI] [PubMed] [Google Scholar]
  4. Duff R., Rapp F. Properties of hamster embryo fibroblasts transformed in vitro after exposure to ultraviolet-irradiated herpes simplex virus type 2. J Virol. 1971 Oct;8(4):469–477. doi: 10.1128/jvi.8.4.469-477.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Galloway D. A., McDougall J. K. Transformation of rodent cells by a cloned DNA fragment of herpes simplex virus type 2. J Virol. 1981 May;38(2):749–760. doi: 10.1128/jvi.38.2.749-760.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hayashi Y., Iwasaka T., Smith C. C., Aurelian L., Lewis G. K., Ts'o P. O. Multistep transformation by defined fragments of herpes simplex virus type 2 DNA: oncogenic region and its gene product. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8493–8497. doi: 10.1073/pnas.82.24.8493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  8. Jariwalla R. J., Aurelian L., Ts'o P. O. Immortalization and neoplastic transformation of normal diploid cells by defined cloned DNA fragments of herpes simplex virus type 2. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5902–5906. doi: 10.1073/pnas.80.19.5902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jariwalla R. J., Aurelian L., Ts'o P. O. Neoplastic transformation of cultured Syrian hamster embryo cells by DNA of herpes simplex virus type 2. J Virol. 1979 Apr;30(1):404–409. doi: 10.1128/jvi.30.1.404-409.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jariwalla R. J., Aurelian L., Ts'o P. O. Tumorigenic transformation induced by a specific fragment of DNA from herpes simplex virus type 2. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2279–2283. doi: 10.1073/pnas.77.4.2279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kucera L. S., Gusdon J. P., Edwards I., Herbst G. Oncogenic transformation of rat embryo fibroblasts with photoinactivated herpes simplex virus: rapid in vitro cloning of transformed cells. J Gen Virol. 1977 Jun;35(3):473–485. doi: 10.1099/0022-1317-35-3-473. [DOI] [PubMed] [Google Scholar]
  12. Leavitt J., Gunning P., Kedes L., Jariwalla R. Smooth muscle alpha-action is a transformation-sensitive marker for mouse NIH 3T3 and Rat-2 cells. 1985 Aug 29-Sep 4Nature. 316(6031):840–842. doi: 10.1038/316840a0. [DOI] [PubMed] [Google Scholar]
  13. Macnab J. C. Transformation of rat embryo cells by temperature-sensitive mutants of herpes simplex virus. J Gen Virol. 1974 Jul;24(1):143–153. doi: 10.1099/0022-1317-24-1-143. [DOI] [PubMed] [Google Scholar]
  14. McLauchlan J., Clements J. B. DNA sequence homology between two co-linear loci on the HSV genome which have different transforming abilities. EMBO J. 1983;2(11):1953–1961. doi: 10.1002/j.1460-2075.1983.tb01684.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Peden K., Mounts P., Hayward G. S. Homology between mammalian cell DNA sequences and human herpesvirus genomes detected by a hybridization procedure with high-complexity probe. Cell. 1982 Nov;31(1):71–80. doi: 10.1016/0092-8674(82)90406-8. [DOI] [PubMed] [Google Scholar]
  16. Reyes G. R., LaFemina R., Hayward S. D., Hayward G. S. Morphological transformation by DNA fragments of human herpesviruses: evidence for two distinct transforming regions in herpes simplex virus types 1 and 2 and lack of correlation with biochemical transfer of the thymidine kinase gene. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):629–641. doi: 10.1101/sqb.1980.044.01.066. [DOI] [PubMed] [Google Scholar]
  17. Shih C., Weinberg R. A. Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell. 1982 May;29(1):161–169. doi: 10.1016/0092-8674(82)90100-3. [DOI] [PubMed] [Google Scholar]
  18. Topp W. C. Normal rat cell lines deficient in nuclear thymidine kinase. Virology. 1981 Aug;113(1):408–411. doi: 10.1016/0042-6822(81)90168-9. [DOI] [PubMed] [Google Scholar]
  19. Wilkie N. M., Clements J. B., Macnab J. C., Subak-Sharpe J. H. The structure and biological properties of herpes simplex virus DNA. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):657–666. doi: 10.1101/sqb.1974.039.01.079. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES