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. 1986 Jun;83(11):3997–4001. doi: 10.1073/pnas.83.11.3997

Transforming gene from human stomach cancers and a noncancerous portion of stomach mucosa.

H Sakamoto, M Mori, M Taira, T Yoshida, S Matsukawa, K Shimizu, M Sekiguchi, M Terada, T Sugimura
PMCID: PMC323652  PMID: 3459165

Abstract

DNAs from 21 human stomach cancers, 16 metastatic stomach cancers to lymph nodes, and 21 apparently noncancerous specimens of stomach mucosae from a total of 26 patients with stomach cancer were tested for their ability to induce neoplastic transformation of NIH 3T3 cells on transfection by the calcium phosphate precipitation technique. Three samples of DNA were shown to have transforming activity; one was from a primary stomach cancer of one patient, the second was from a noncancerous portion of stomach mucosa of the same patient, and the third was from a lymph node metastasis of stomach cancer from another patient. These transformants were tumorigenic in nude mice, and DNAs from the cells could induce secondary transformants. A portion of the transforming gene from the stomach cancer of one patient, which contained the sequences expressed in the NIH 3T3 transformants, was cloned. The transforming gene did not have any homology with the transforming sequences reported previously. We have applied the term hst to this novel human transforming gene. The transforming gene, hst, was found to be present in all the primary and secondary transformants induced by the other two samples of DNA.

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Selected References

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

  1. Albino A. P., Le Strange R., Oliff A. I., Furth M. E., Old L. J. Transforming ras genes from human melanoma: a manifestation of tumour heterogeneity? Nature. 1984 Mar 1;308(5954):69–72. doi: 10.1038/308069a0. [DOI] [PubMed] [Google Scholar]
  2. Bos J. L., Toksoz D., Marshall C. J., Verlaan-de Vries M., Veeneman G. H., van der Eb A. J., van Boom J. H., Janssen J. W., Steenvoorden A. C. Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia. 1985 Jun 27-Jul 3Nature. 315(6022):726–730. doi: 10.1038/315726a0. [DOI] [PubMed] [Google Scholar]
  3. Cooper C. S., Park M., Blair D. G., Tainsky M. A., Huebner K., Croce C. M., Vande Woude G. F. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature. 1984 Sep 6;311(5981):29–33. doi: 10.1038/311029a0. [DOI] [PubMed] [Google Scholar]
  4. Cooper G. M., Lane M. A. Cellular transforming genes and oncogenesis. Biochim Biophys Acta. 1984;738(1-2):9–20. doi: 10.1016/0304-419x(84)90017-9. [DOI] [PubMed] [Google Scholar]
  5. Duesberg P. H. Activated proto-onc genes: sufficient or necessary for cancer? Science. 1985 May 10;228(4700):669–677. doi: 10.1126/science.3992240. [DOI] [PubMed] [Google Scholar]
  6. Eva A., Aaronson S. A. Isolation of a new human oncogene from a diffuse B-cell lymphoma. Nature. 1985 Jul 18;316(6025):273–275. doi: 10.1038/316273a0. [DOI] [PubMed] [Google Scholar]
  7. Fasano O., Birnbaum D., Edlund L., Fogh J., Wigler M. New human transforming genes detected by a tumorigenicity assay. Mol Cell Biol. 1984 Sep;4(9):1695–1705. doi: 10.1128/mcb.4.9.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fujita J., Srivastava S. K., Kraus M. H., Rhim J. S., Tronick S. R., Aaronson S. A. Frequency of molecular alterations affecting ras protooncogenes in human urinary tract tumors. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3849–3853. doi: 10.1073/pnas.82.11.3849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fujita J., Yoshida O., Yuasa Y., Rhim J. S., Hatanaka M., Aaronson S. A. Ha-ras oncogenes are activated by somatic alterations in human urinary tract tumours. 1984 May 31-Jun 6Nature. 309(5967):464–466. doi: 10.1038/309464a0. [DOI] [PubMed] [Google Scholar]
  10. Fukui M., Yamamoto T., Kawai S., Maruo K., Toyoshima K. Detection of a raf-related and two other transforming DNA sequences in human tumors maintained in nude mice. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5954–5958. doi: 10.1073/pnas.82.17.5954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goubin G., Goldman D. S., Luce J., Neiman P. E., Cooper G. M. Molecular cloning and nucleotide sequence of a transforming gene detected by transfection of chicken B-cell lymphoma DNA. Nature. 1983 Mar 10;302(5904):114–119. doi: 10.1038/302114a0. [DOI] [PubMed] [Google Scholar]
  12. Jelinek W. R., Toomey T. P., Leinwand L., Duncan C. H., Biro P. A., Choudary P. V., Weissman S. M., Rubin C. M., Houck C. M., Deininger P. L. Ubiquitous, interspersed repeated sequences in mammalian genomes. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1398–1402. doi: 10.1073/pnas.77.3.1398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  14. Newbold R. F., Overell R. W. Fibroblast immortality is a prerequisite for transformation by EJ c-Ha-ras oncogene. Nature. 1983 Aug 18;304(5927):648–651. doi: 10.1038/304648a0. [DOI] [PubMed] [Google Scholar]
  15. Oshimura M., Gilmer T. M., Barrett J. C. Nonrandom loss of chromosome 15 in Syrian hamster tumours induced by v-Ha-ras plus v-myc oncogenes. Nature. 1985 Aug 15;316(6029):636–639. doi: 10.1038/316636a0. [DOI] [PubMed] [Google Scholar]
  16. Padua R. A., Barrass N., Currie G. A. A novel transforming gene in a human malignant melanoma cell line. Nature. 1984 Oct 18;311(5987):671–673. doi: 10.1038/311671a0. [DOI] [PubMed] [Google Scholar]
  17. Parkin D. M., Stjernswärd J., Muir C. S. Estimates of the worldwide frequency of twelve major cancers. Bull World Health Organ. 1984;62(2):163–182. [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Prassolov V. S., Sakamoto H., Nishimura S., Terada M., Sugimura T. Activation of c-Ki-ras gene in human pancreatic cancer. Jpn J Cancer Res. 1985 Sep;76(9):792–795. [PubMed] [Google Scholar]
  20. Pulciani S., Santos E., Lauver A. V., Long L. K., Aaronson S. A., Barbacid M. Oncogenes in solid human tumours. Nature. 1982 Dec 9;300(5892):539–542. doi: 10.1038/300539a0. [DOI] [PubMed] [Google Scholar]
  21. Ruley H. E. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature. 1983 Aug 18;304(5927):602–606. doi: 10.1038/304602a0. [DOI] [PubMed] [Google Scholar]
  22. Santos E., Martin-Zanca D., Reddy E. P., Pierotti M. A., Della Porta G., Barbacid M. Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient. Science. 1984 Feb 17;223(4637):661–664. doi: 10.1126/science.6695174. [DOI] [PubMed] [Google Scholar]
  23. Schechter A. L., Stern D. F., Vaidyanathan L., Decker S. J., Drebin J. A., Greene M. I., Weinberg R. A. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984 Dec 6;312(5994):513–516. doi: 10.1038/312513a0. [DOI] [PubMed] [Google Scholar]
  24. Shimizu K., Nakatsu Y., Sekiguchi M., Hokamura K., Tanaka K., Terada M., Sugimura T. Molecular cloning of an activated human oncogene, homologous to v-raf, from primary stomach cancer. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5641–5645. doi: 10.1073/pnas.82.17.5641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Takahashi M., Ritz J., Cooper G. M. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1985 Sep;42(2):581–588. doi: 10.1016/0092-8674(85)90115-1. [DOI] [PubMed] [Google Scholar]
  27. Weinberg R. A. Oncogenes of spontaneous and chemically induced tumors. Adv Cancer Res. 1982;36:149–163. doi: 10.1016/s0065-230x(08)60424-8. [DOI] [PubMed] [Google Scholar]
  28. 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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