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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
. 1982 Jun;79(11):3637–3640. doi: 10.1073/pnas.79.11.3637

Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses.

C J Der, T G Krontiris, G M Cooper
PMCID: PMC346478  PMID: 6285355

Abstract

Blot hybridization analysis indicated that NIH 3T3 mouse bladder transformed by high molecular weight DNAs of a human bladder and a human lung carcinoma cell line contained new sequences homologous, respectively, to the transforming genes of Harvey (rasH) and Kirsten (rasK) sarcoma viruses. The unique ras sequences were present in multiple independent NIH cell lines transformed in both primary and secondary transfection assays and corresponded to ras sequences normally present in human DNAs. The ras gene product was expressed in NIH cells transformed by bladder carcinoma DNAs and in the human bladder carcinoma cell lines at levels 2- to 4-fold greater than the level observed in nontransformed NIH 3T3 cells. These results indicate that the transforming genes of these human tumor cell lines are the cellular homologs of two retroviral transforming genes.

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Selected References

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  1. Bishop J. M. Enemies within: the genesis of retrovirus oncogenes. Cell. 1981 Jan;23(1):5–6. doi: 10.1016/0092-8674(81)90263-4. [DOI] [PubMed] [Google Scholar]
  2. Blair D. G., Oskarsson M., Wood T. G., McClements W. L., Fischinger P. J., Vande Woude G. G. Activation of the transforming potential of a normal cell sequence: a molecular model for oncogenesis. Science. 1981 May 22;212(4497):941–943. doi: 10.1126/science.7233190. [DOI] [PubMed] [Google Scholar]
  3. Coffin J. M., Varmus H. E., Bishop J. M., Essex M., Hardy W. D., Jr, Martin G. S., Rosenberg N. E., Scolnick E. M., Weinberg R. A., Vogt P. K. Proposal for naming host cell-derived inserts in retrovirus genomes. J Virol. 1981 Dec;40(3):953–957. doi: 10.1128/jvi.40.3.953-957.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cooper G. M., Neiman P. E. Transforming genes of neoplasms induced by avian lymphoid leukosis viruses. Nature. 1980 Oct 16;287(5783):656–659. doi: 10.1038/287656a0. [DOI] [PubMed] [Google Scholar]
  5. Cooper G. M., Neiman P. E. Two distinct candidate transforming genes of lymphoid leukosis virus-induced neoplasms. Nature. 1981 Aug 27;292(5826):857–858. doi: 10.1038/292857a0. [DOI] [PubMed] [Google Scholar]
  6. Cooper G. M., Okenquist S., Silverman L. Transforming activity of DNA of chemically transformed and normal cells. Nature. 1980 Apr 3;284(5755):418–421. doi: 10.1038/284418a0. [DOI] [PubMed] [Google Scholar]
  7. Copeland N. G., Zelenetz A. D., Copper G. M. Transformation by subgenomic fragments of Rous sarcoma virus DNA. Cell. 1980 Apr;19(4):863–870. doi: 10.1016/0092-8674(80)90077-x. [DOI] [PubMed] [Google Scholar]
  8. DeFeo D., Gonda M. A., Young H. A., Chang E. H., Lowy D. R., Scolnick E. M., Ellis R. W. Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3328–3332. doi: 10.1073/pnas.78.6.3328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Der C. J., Stanbridge E. J. A tumor-specific membrane phosphoprotein marker in human cell hybrids. Cell. 1981 Nov;26(3 Pt 1):429–438. doi: 10.1016/0092-8674(81)90212-9. [DOI] [PubMed] [Google Scholar]
  10. Ellis R. W., DeFeo D., Maryak J. M., Young H. A., Shih T. Y., Chang E. H., Lowy D. R., Scolnick E. M. Dual evolutionary origin for the rat genetic sequences of Harvey murine sarcoma virus. J Virol. 1980 Nov;36(2):408–420. doi: 10.1128/jvi.36.2.408-420.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ellis R. W., Defeo D., Shih T. Y., Gonda M. A., Young H. A., Tsuchida N., Lowy D. R., Scolnick E. M. The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes. Nature. 1981 Aug 6;292(5823):506–511. doi: 10.1038/292506a0. [DOI] [PubMed] [Google Scholar]
  12. Giovanella B. C., Stehlin J. S., Jr, Williams L. J., Jr, Lee S. S., Shepard R. C. Heterotransplantation of human cancers into nude mice: a model system for human cancer chemotherapy. Cancer. 1978 Nov;42(5):2269–2281. doi: 10.1002/1097-0142(197811)42:5<2269::aid-cncr2820420527>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  13. Goldfarb M. P., Weinberg R. A. Structure of the provirus within NIH 3T3 cells transfected with Harvey sarcoma virus DNA. J Virol. 1981 Apr;38(1):125–135. doi: 10.1128/jvi.38.1.125-135.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hanahan D., Meselson M. Plasmid screening at high colony density. Gene. 1980 Jun;10(1):63–67. doi: 10.1016/0378-1119(80)90144-4. [DOI] [PubMed] [Google Scholar]
  15. Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
  16. Hopkins N., Besmer P., DeLeo A. B., Law L. W. High-frequency cotransfer of the transformed phenotype and a tumor-specific transplantation antigen by DNA from the 3-methylcholanthrene-induced Meth A sarcoma of BALB/c mice. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7555–7559. doi: 10.1073/pnas.78.12.7555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Krontiris T. G., Cooper G. M. Transforming activity of human tumor DNAs. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1181–1184. doi: 10.1073/pnas.78.2.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lane M. A., Sainten A., Cooper G. M. Activation of related transforming genes in mouse and human mammary carcinomas. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5185–5189. doi: 10.1073/pnas.78.8.5185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lane M. A., Sainten A., Cooper G. M. Stage-specific transforming genes of human and mouse B- and T-lymphocyte neoplasms. Cell. 1982 Apr;28(4):873–880. doi: 10.1016/0092-8674(82)90066-6. [DOI] [PubMed] [Google Scholar]
  20. Langbeheim H., Shih T. Y., Scolnick E. M. Identification of a normal vertebrate cell protein related to the p21 src of Harvey murine sarcoma virus. Virology. 1980 Oct 30;106(2):292–300. doi: 10.1016/0042-6822(80)90252-4. [DOI] [PubMed] [Google Scholar]
  21. Maniatis T., Jeffrey A., Kleid D. G. Nucleotide sequence of the rightward operator of phage lambda. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1184–1188. doi: 10.1073/pnas.72.3.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Murray M. J., Shilo B. Z., Shih C., Cowing D., Hsu H. W., Weinberg R. A. Three different human tumor cell lines contain different oncogenes. Cell. 1981 Aug;25(2):355–361. doi: 10.1016/0092-8674(81)90054-4. [DOI] [PubMed] [Google Scholar]
  23. Perucho M., Goldfarb M., Shimizu K., Lama C., Fogh J., Wigler M. Human-tumor-derived cell lines contain common and different transforming genes. Cell. 1981 Dec;27(3 Pt 2):467–476. doi: 10.1016/0092-8674(81)90388-3. [DOI] [PubMed] [Google Scholar]
  24. Shih C., Padhy L. C., Murray M., Weinberg R. A. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature. 1981 Mar 19;290(5803):261–264. doi: 10.1038/290261a0. [DOI] [PubMed] [Google Scholar]
  25. Shih C., Shilo B. Z., Goldfarb M. P., Dannenberg A., Weinberg R. A. Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5714–5718. doi: 10.1073/pnas.76.11.5714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shilo B. Z., Weinberg R. A. Unique transforming gene in carcinogen-transformed mouse cells. Nature. 1981 Feb 12;289(5798):607–609. doi: 10.1038/289607a0. [DOI] [PubMed] [Google Scholar]
  27. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  28. Tsuchida N., Uesugi S. Structure and functions of the Kirsten murine sarcoma virus genome: molecular cloning of biologically active Kirsten murine sarcoma virus DNA. J Virol. 1981 May;38(2):720–727. doi: 10.1128/jvi.38.2.720-727.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wigler M., Sweet R., Sim G. K., Wold B., Pellicer A., Lacy E., Maniatis T., Silverstein S., Axel R. Transformation of mammalian cells with genes from procaryotes and eucaryotes. Cell. 1979 Apr;16(4):777–785. doi: 10.1016/0092-8674(79)90093-x. [DOI] [PubMed] [Google Scholar]

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