pmc logo imageJournal ListSearchpmc logo image
Logo of molcellbMol Cell Biol SubscriptionsMol Cell Biol Web Site
Mol Cell Biol. 1986 February; 6(2): 502–510.
PMCID: PMC367539
Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene.
G Casey, R Smith, D McGillivray, G Peters, and C Dickson
Abstract
int-2 is one of two cellular genes (int-1 and int-2) currently implicated in the genesis of mammary carcinomas by mouse mammary tumor virus and may constitute a novel cellular proto-oncogene. Using low-stringency hybridization with mouse int-2 probes, we established that homologous genes exist in a variety of mammalian species, including humans, but failed to detect related sequences in other classes and phyla. Recombinant bacteriophage clones and a single cosmid encompassing the human int-2 gene were isolated and characterized by restriction enzyme mapping. A survey of nine primary human breast tumors, three breast tumor cell lines, and three normal individuals revealed no evidence for gross amplification or rearrangement of the int-2 locus. Three distinct restriction fragment length polymorphisms were observed which could prove useful in future linkage studies. By a combination of in situ hybridization of metaphase chromosomes and somatic cell genetics, the human int-2 gene was mapped to chromosome 11, band q13.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Images in this article
Click on the image to see a larger version.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
  • Bishop, JM. Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983;52:301–354. [PubMed]
  • Corcoran, LM; Adams, JM; Dunn, AR; Cory, S. Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion. Cell. 1984 May;37(1):113–122. [PubMed]
  • DeFeo-Jones, D; Scolnick, EM; Koller, R; Dhar, R. ras-Related gene sequences identified and isolated from Saccharomyces cerevisiae. Nature. 306(5944):707–709. [PubMed]
  • de Martinville, B; Giacalone, J; Shih, C; Weinberg, RA; Francke, U. Oncogene from human EJ bladder carcinoma is located on the short arm of chromosome 11. Science. 1983 Feb 4;219(4584):498–501. [PubMed]
  • Der, CJ; Krontiris, TG; Cooper, GM. Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3637–3640. [PubMed]
  • Dickson, C; Smith, R; Brookes, S; Peters, G. Tumorigenesis by mouse mammary tumor virus: proviral activation of a cellular gene in the common integration region int-2. Cell. 1984 Jun;37(2):529–536. [PubMed]
  • Erikson, J; Finan, J; Tsujimoto, Y; Nowell, PC; Croce, CM. The chromosome 14 breakpoint in neoplastic B cells with the t(11;14) translocation involves the immunoglobulin heavy chain locus. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4144–4148. [PubMed]
  • Fung, YK; Fadly, AM; Crittenden, LB; Kung, HJ. On the mechanism of retrovirus-induced avian lymphoid leukosis: deletion and integration of the proviruses. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3418–3422. [PubMed]
  • Fung, YK; Lewis, WG; Crittenden, LB; Kung, HJ. Activation of the cellular oncogene c-erbB by LTR insertion: molecular basis for induction of erythroblastosis by avian leukosis virus. Cell. 1983 Jun;33(2):357–368. [PubMed]
  • Gallwitz, D; Donath, C; Sander, C. A yeast gene encoding a protein homologous to the human c-has/bas proto-oncogene product. Nature. 306(5944):704–707. [PubMed]
  • Goldfarb, M; Shimizu, K; Perucho, M; Wigler, M. Isolation and preliminary characterization of a human transforming gene from T24 bladder carcinoma cells. Nature. 1982 Apr 1;296(5856):404–409. [PubMed]
  • Goodfellow, PN; Banting, G; Wiles, MV; Tunnacliffe, A; Parkar, M; Solomon, E; Dalchau, R; Fabre, JW. The gene, MIC4, which controls expression of the antigen defined by monoclonal antibody F10.44.2, is on human chromosome 11. Eur J Immunol. 1982 Aug;12(8):659–663. [PubMed]
  • Graf, T; Beug, H. Role of the v-erbA and v-erbB oncogenes of avian erythroblastosis virus in erythroid cell transformation. Cell. 1983 Aug;34(1):7–9. [PubMed]
  • Harper, ME; Ullrich, A; Saunders, GF. Localization of the human insulin gene to the distal end of the short arm of chromosome 11. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4458–4460. [PubMed]
  • Hayward, WS; Neel, BG; Astrin, SM. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. [PubMed]
  • Hope, RM; Goodfellow, PN; Solomon, E; Bodmer, WF. Identification of MIC5, a human X-linked gene controlling expression of a cell surface antigen: definition by a monoclonal antibody raised against a human X mouse somatic cell hybrid. Cytogenet Cell Genet. 1982;33(3):204–212. [PubMed]
  • Huerre, C; Despoisse, S; Gilgenkrantz, S; Lenoir, GM; Junien, C. c-Ha-ras1 is not deleted in aniridia-Wilms' tumour association. Nature. 305(5935):638–641. [PubMed]
  • Jones, C; Bill, J; Larizza, L; Pym, B; Goodfellow, P; Tunnacliffe, A. Relationships between genes on human chromosome 11 encoding cell-surface antigens. Somat Cell Mol Genet. 1984 Jul;10(4):423–428. [PubMed]
  • Kozak, CA; Sears, JF; Hoggan, MD. Genetic mapping of the mouse oncogenes c-Ha-ras-1 and c-fes to chromosome 7. J Virol. 1983 Jul;47(1):217–220. [PubMed]
  • Lindenmaier, W; Hauser, H; de Wilke, IG; Schütz, G. Gene shuttling: moving of cloned DNA into and out of eukaryotic cells. Nucleic Acids Res. 1982 Feb 25;10(4):1243–1256. [PubMed]
  • Malcolm, S; Barton, P; Murphy, C; Ferguson-Smith, MA. Chromosomal localization of a single copy gene by in situ hybridization--human beta globin genes on the short arm of chromosome 11. Ann Hum Genet. 1981 May;45(Pt 2):135–141. [PubMed]
  • McCoy, MS; Toole, JJ; Cunningham, JM; Chang, EH; Lowy, DR; Weinberg, RA. Characterization of a human colon/lung carcinoma oncogene. Nature. 1983 Mar 3;302(5903):79–81. [PubMed]
  • Neil, JC; Hughes, D; McFarlane, R; Wilkie, NM; Onions, DE; Lees, G; Jarrett, O. Transduction and rearrangement of the myc gene by feline leukaemia virus in naturally occurring T-cell leukaemias. Nature. 308(5962):814–820. [PubMed]
  • Nusse, R; van Ooyen, A; Cox, D; Fung, YK; Varmus, H. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature. 307(5947):131–136. [PubMed]
  • Nusse, R; Varmus, HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982 Nov;31(1):99–109. [PubMed]
  • Parada, LF; Tabin, CJ; Shih, C; Weinberg, RA. Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature. 1982 Jun 10;297(5866):474–478. [PubMed]
  • Payne, GS; Bishop, JM; Varmus, HE. Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas. Nature. 1982 Jan 21;295(5846):209–214. [PubMed]
  • Perry, RP. Consequences of myc invasion of immunoglobulin loci: facts and speculation. Cell. 1983 Jul;33(3):647–649. [PubMed]
  • Peters, G; Brookes, S; Smith, R; Dickson, C. Tumorigenesis by mouse mammary tumor virus: evidence for a common region for provirus integration in mammary tumors. Cell. 1983 Jun;33(2):369–377. [PubMed]
  • Peters, G; Kozak, C; Dickson, C. Mouse mammary tumor virus integration regions int-1 and int-2 map on different mouse chromosomes. Mol Cell Biol. 1984 Feb;4(2):375–378. [PubMed]
  • Santos, E; Tronick, SR; Aaronson, SA; Pulciani, S; Barbacid, M. T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes. Nature. 1982 Jul 22;298(5872):343–347. [PubMed]
  • Selten, G; Cuypers, HT; Zijlstra, M; Melief, C; Berns, A. Involvement of c-myc in MuLV-induced T cell lymphomas in mice: frequency and mechanisms of activation. EMBO J. 1984 Dec 20;3(13):3215–3222. [PubMed]
  • Shilo, BZ; Weinberg, RA. DNA sequences homologous to vertebrate oncogenes are conserved in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6789–6792. [PubMed]
  • Steffen, D. Proviruses are adjacent to c-myc in some murine leukemia virus-induced lymphomas. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2097–2101. [PubMed]
  • Tsujimoto, Y; Jaffe, E; Cossman, J; Gorham, J; Nowell, PC; Croce, CM. Clustering of breakpoints on chromosome 11 in human B-cell neoplasms with the t(11;14) chromosome translocation. Nature. 315(6017):340–343. [PubMed]
  • Tsujimoto, Y; Yunis, J; Onorato-Showe, L; Erikson, J; Nowell, PC; Croce, CM. Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation. Science. 1984 Jun 29;224(4656):1403–1406. [PubMed]
  • Tunnacliffe, A; Goodfellow, P; Banting, G; Solomon, E; Knowles, BB; Andrews, P. Human chromosome 11 carries at least four genes controlling expression of cell-surface antigens. Somatic Cell Genet. 1983 Sep;9(5):629–642. [PubMed]
  • van Ooyen, A; Nusse, R. Structure and nucleotide sequence of the putative mammary oncogene int-1; proviral insertions leave the protein-encoding domain intact. Cell. 1984 Nov;39(1):233–240. [PubMed]
  • van 't Veer, LJ; van Kessel, AG; van Heerikhuizen, H; van Ooyen, A; Nusse, R. Molecular cloning and chromosomal assignment of the human homolog of int-1, a mouse gene implicated in mammary tumorigenesis. Mol Cell Biol. 1984 Nov;4(11):2532–2534. [PubMed]
  • Varmus, HE. The molecular genetics of cellular oncogenes. Annu Rev Genet. 1984;18:553–612. [PubMed]