Oncogenes and Breast Cancer Progression

  • Robert Callahan
Part of the Basic Life Sciences book series (BLSC, volume 57)


The etiology of breast cancer is thought to involve a complex interplay of genetic, hormonal, and dietary factors that are superimposed on the physiological status of the host. Extensive studies have been undertaken to determine the relationship between these factors and tumor development in humans and experimental rodent models. Attempts to develop a cohesive picture of how these factors participate in mammary tumorigenesis have been hampered, in part, by a lack of information on the specific genetic lesions that contribute to the initiation and/or evolution of tumor development.


Mammary Gland Mammary Tumor Long Terminal Repeat Human Breast Carcinoma Mouse Mammary Tumor Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. S. A. Aaronson, and S. R. Tronick, 1985, The role of oncogenes in human neoplasia, in: “Important Advances in Oncology 1985,” V. T. DeVita, S. Hellman, S. A. Rosenberg, eds., J. B. Lippincott Company, Philadelphia.Google Scholar
  2. R. W. Alexander, C. Moscovici, and P. K. Vogt, 1979, Avian oncovirus Mill Hill No. 2: pathogenicity in chickens, J. Natl. Cancer Inst. 62:359–366.PubMedGoogle Scholar
  3. I. U. Ali, R. Lidereau, C. Thiellet, and R. Callahan, 1987, Reduction to homozygosity of genes on chromosome 11 in human breast neoplasia, Science 238:185–188.PubMedCrossRefGoogle Scholar
  4. I. U. Ali, R. Lidereau, and R. Callahan, 1988a, Heterogeneity of genetic alterations in primary human breast tumors, in: “Breast Cancer: Cellular and Molecular Biology,” M. E. Lippman and R. B. Dickson, eds., Martinus Nijhoff Publishers, Boston.Google Scholar
  5. I. U. Ali, G. Campbell, R. Lidereau, and R. Callahan, 1988b, Amplification of c-erb B-2 and aggressive human breast tumors?, Science 240:1795–1796.CrossRefGoogle Scholar
  6. I. U. Ali, G. Campbell, R. Lidereau, and R. Callahan, 1988c, Lack of evidence for the prognostic significance of c-erb B-2 amplification in human breast carcinoma, Oncogene Res. 3:139–146.PubMedGoogle Scholar
  7. I. U. Ali and R. Callahan, 1988, Prognostic significance of genetic alterations in human breast carcinoma, in: “Molecular Genetics and the Diagnosis of Cancer,” J. Cossman, ed., Elsevier Science Pub., New York (In press).Google Scholar
  8. I. U. Ali, G. Merlo, R. Lidereau, and R. Callahan, 1988d, The amplification unit on chromosome 11q13 in aggressive primary human breast tumors contains the bcl-1, int-1, and hst loci, Oncogene, (In press).Google Scholar
  9. I. U. Ali, S. Meissner, R. Lidereau, and R. Callahan, 1988e, Allelic deletion of c-erb A-2 proto-oncogene in human breast carcinoma signifies a possible recessive mutation in member(s) of steroid/thyroid hormone receptor family, (Manuscript in preparation).Google Scholar
  10. I. U. Ali, S. Miessner, N. Spurr, and R. Callahan, 1988f, Mapping of the c-erb A-2 proto-oncogene to chromosome 3p and its homology with the thyroid hormone receptor gene, (Manuscript in preparation).Google Scholar
  11. A. C. Andres, C. A. Schonenberger, B. Groner, L. Hennighausen, M. LeMaur, and P. Gerlinger, 1987, Ha ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice, Proc. Natl. Acad. Sci. USA 84:1299–1303.PubMedCrossRefGoogle Scholar
  12. C. I. Bargmann, M. C. Hung, and R. A. Weinberg, 1986, Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185, Cell 45:649–657.PubMedCrossRefGoogle Scholar
  13. M. S. Berger, G. W. Locher, S. Saurer, W. J. Gullick, M. D. Waterfield, B. Groner, and N. E. Hynes, 1988, Correlation of c-erb B-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading, Cancer Res. 48:1238–1243.PubMedGoogle Scholar
  14. J. Bishop, 1985, Viral oncogenes, Cell 42:23–38.PubMedCrossRefGoogle Scholar
  15. J. J. Bitner, 1942, The milk influence of breast tumors in mice, Science 94:462–463.CrossRefGoogle Scholar
  16. M. Bonilla, M. Ramirez, J. Lopez-Cueto, and P. Gariglio, 1988, In vivo amplification and rearrangement of c-myc oncogene in human breast tumors, J. Natl. Cancer Inst. 80:665–671.PubMedCrossRefGoogle Scholar
  17. A. M. C. Brown, J. Papkoff, Y. K. T. Fung, G. M. Shackleford, and H. E. Varmus, 1987, Identification of protein products encoded by the protooncogene int-1, Mol. Cell. Biol. 7:3971–3981.PubMedGoogle Scholar
  18. R. Callahan, 1987, Retrovirus and proto-oncogene involvement in the etiology of breast neoplasia, in: “The Mammary Gland,” M. C. Neville and C. W. Daniel, eds., Plenum Publishing Company, New York.Google Scholar
  19. M. J. Cline, H. Battifora, and J. Yokota, 1987, Proto-oncogene abnormalities in human breast cancer: correlation with anatomic features and clinical course of disease, J. Clin. Oncol. 5:999–1010.PubMedGoogle Scholar
  20. P. Delli Bovi, A. M. Curatola, F. G. Kern, A. Greco, M. Ittmann, and C. Basilico, 1987, An oncogene isolated by transfection of Kaposi’s sarcoma DNA encodes a growth factor that is a member of the FGF family, Cell 50:729–740.PubMedCrossRefGoogle Scholar
  21. K. B. DeOme, L. J. Faultein, H. H. Bern, and P. B. Blair, 1959, Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland free mammary fat pads of female C3H mice, Cancer Res. 19:515–520.PubMedGoogle Scholar
  22. C. Dickson and G. Peters, 1987, Potential oncogene product related to growth factors, Nature 326:833–836.PubMedCrossRefGoogle Scholar
  23. C. Dickson, R. Smith, S. Brookes, and G. Peters, 1984, Tumorigenesis by mouse mammary tumor virus: proviral activation of a cellular gene in the common integration region int-2, Cell 37:539–550.CrossRefGoogle Scholar
  24. C. Escot, C. Theillet, R. Lidereau, F. Spyratos, M. H. Champeme, J. Gest, and R. Callahan, 1986, Genetic alteration of the c-myc proto-oncogene in human primary breast carcinoma, Proc. Natl. Acad. Sci. USA 83:4834–4838.PubMedCrossRefGoogle Scholar
  25. L. Foulds, 1949, Mammary tumors in hybrid mice: The presence and transmission of the mammary tumor agent, Br. J. Cancer 3:230–239.PubMedCrossRefGoogle Scholar
  26. Y. K. T. Fung, G. M. Shackleford, A. M. C. Brown, G. S. Sanders, and H. E. Varmus, 1985, Nucleotide sequence and expression in vitro of cDNA derived from mRNA of int-1, a provirally activated mouse mammary oncogene, Mol. Cell. Biol. 5:3337–3348.PubMedGoogle Scholar
  27. D. Gallahan and R. Callahan, 1986, A new common integration region (int-3) for the mouse mammary tumor virus on mouse chromosome 17, J. Virol. 61:218–220.Google Scholar
  28. D. Gospodarowicz, G. Neufeld, and L. Schweigerer, 1986, Fibroblast growth factor, Mol. Cell. Endocrinol. 46:187–204.PubMedCrossRefGoogle Scholar
  29. D. Gospodarowicz, N. Ferrara, L. Schweiger, and G. Newfeld, 1987, Structural characterization and biological functions of fibroblast growth factor, Endocrine Rev. 8:95–114.CrossRefGoogle Scholar
  30. S. Green and P. Chambon, 1986, A superfamily of potentially oncogenic hormone receptors, Nature 324:615–620.PubMedCrossRefGoogle Scholar
  31. A. Jakobovits, G. M. Shackleford, H. E. Varmus, and G. R. Martin, 1986, Two proto-oncogenes implicated in mammary carcinogenesis, int-1 and int-2, are independently regulated during mouse development, Proc. Natl. Acad. Sci. USA 83:7806–7810.PubMedCrossRefGoogle Scholar
  32. M. Kaebling and H. P. Klinger, 1985, Suppression of tumorigenicity in somatic cell hybrids. III. Cosegregation of human chromosome 11 of a normal cell and suppression of tumorigenicity in intraspecies hybrids of normal diploid x malignant cells, Cytogenet. Cell Genet. 41:65–70.CrossRefGoogle Scholar
  33. G. Klein, 1981, The role of gene dosage and genetic transposition in carcinogenesis, Nature 294:290–293.CrossRefGoogle Scholar
  34. A. G. Knudson, 1971, Mutation and cancer: statistical study of retinoblastoma, Proc. Natl. Acad. Sci USA 68:820–823.PubMedCrossRefGoogle Scholar
  35. H. Land, L. Parada, and R. A. Weinberg, 1983, Cellular oncogenes and multistep carcinogenesis, Nature 304:596–602.PubMedCrossRefGoogle Scholar
  36. A. Leder, P. K. Pattengale, A. Kuo, T. A. Stewart, and P. Leder, 1986, Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development, Cell 45:485–495.PubMedCrossRefGoogle Scholar
  37. E. Lee, Y.-H. P. H. To, J.-Y. Shew, R. Bookstein, P. Scully, and W.-H. Lee, 1988, Inactivation of the retinoblastoma susceptibility gene in human breast cancers, Science 241:218–222.PubMedCrossRefGoogle Scholar
  38. A. B. Lee, 1968, Genetic and viral influences on mammary tumors in BR6 mice, Br. J. Cancer 22:77–82.PubMedCrossRefGoogle Scholar
  39. R. Lidereau, R. Callahan, C. Dickson, G. Peters, C. Escot, and I. U. Ali, 1988, Amplification of the int-2 gene in primary human breast tumors, Oncogene Res. 2:285–291.PubMedGoogle Scholar
  40. C. Lundberg, L. Skoog, W. K. Cavenee, and M. Nordenskjöld, 1987, Loss of heterozygosity in human ductal breast tumors indicates a recessive mutation on chromosome 13, Proc. Natl. Acad. Sci. USA 84:2373–2376.CrossRefGoogle Scholar
  41. R. Mariani-Costantini, C. Escot, C. Theillet, A. Gentile, G. Merlo, R. Lidereau, and R. Callahan, 1988, In situ myc expression and genomic status of the c-myc locus in infiltrating ductal carcinomas of the breast, Cancer Res. 48:199–205.PubMedGoogle Scholar
  42. R. Moore, G. Casey, S. Brookes, M. Dixon, G. Peters, and C. Dickson, 1986, Sequence, topography and protein coding potential of mouse int-2: a putative oncogene activated by mouse mammary tumor virus. EMBO J 5:919–924.PubMedGoogle Scholar
  43. W. J. Muller, E. Sinn, P. K. Pattengale, R. Wallace, and P. Leder, 1988, Single step induction of mammary adenocarcinoma in transgenic mice bearing activated c-neu oncogene, Cell 54:105–115.PubMedCrossRefGoogle Scholar
  44. S. Nandi, 1963, New method for detection of mouse mammary tumor virus. I. Influence of foster nursing on the incidence of hyperplastic mammary nodules on BALB/c Crg 1 mice, J. Natl. Cancer Inst. 31:57–73.PubMedGoogle Scholar
  45. R. Nusse, 1988, The int genes in mammary tumorigenesis and in normal development, Trends in Genetics (In press).Google Scholar
  46. R. Nusse, and H. Varmus, 1982, Mammary tumor induced by the mouse mammary tumor virus: evidence for a common region for provirus integration in the same region of the host genome, Cell 31:99–109.PubMedCrossRefGoogle Scholar
  47. J. Papkoff, A. M. C. Brown, and H. E. Varmus, 1987, The int-1 proto-oncogene products are glycoproteins that appear to enter the secretory pathway, Mol. Cell Biol. 7:3978.PubMedGoogle Scholar
  48. G. Peters, S. Brookes, R. Smith, and C. Dickson, 1983, Tumorigenesis by mouse mammary tumor virus: evidence for a common region for provirus integration in mammary tumors, Cell 33:369.PubMedCrossRefGoogle Scholar
  49. G. Peters, C. Kozak, and C. Dickson, 1984a, Mouse mammary tumor virus integration region int-1 and int-2 map on different mouse chromosomes, Mol. Cell Biol. 4:375.PubMedGoogle Scholar
  50. G. Peters, A. E. Lee, and C. Dickson, 1984b, Activation of cellular gene by mouse mammary tumor virus may occur early in mammary tumor development, Nature 309:273.PubMedCrossRefGoogle Scholar
  51. T. H. Rabbitts, 1985, The c-myc proto-oncogene: involvement in chromosomal abnormalities, Trends In Genetics 1:327–331.CrossRefGoogle Scholar
  52. U. R. Rapp, F. H. Reynolds, and J. R. Stephenson, 1983, New mammalian transforming retrovirus: demonstration of a polyprotein gene product, J. Virol. 45:914–922.PubMedGoogle Scholar
  53. S. H. Rider, P. A. Gorman, J. M. Shipley, G. Moore, B. Vennström, E. Solomon, and D. Sheer, 1987, Localization of the oncogene c-erb A-2 to human chromosome 3, Ann. Hum. Genet. 51:53–156.CrossRefGoogle Scholar
  54. F. Rijsewijk, M. van Lohuizen, A. van Ooyen, and R. Nusse, 1986, Construction of a retroviral cDNA version of the int-1 mammary oncogene and its expression in vitro, Nucleic Acids Res. 14:693–670.PubMedCrossRefGoogle Scholar
  55. F. Rijsewijk, L. van Deemter, E. Wagenaar, A. Sonnenberg, and R. Nusse, 1987a, Transfection of the int-1 mammary oncogene in cuboidal RAC mammary cell line results in morphological transformation and tumorigenicity, EMBO J. 6:127–131.PubMedGoogle Scholar
  56. F. Rijsewijk, M. Schuerman, L. Wagenaar, P. Parren, D. Weigel, and R. Nusse, 1987b, The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity mutant wingless, Cell 50:649–659.PubMedCrossRefGoogle Scholar
  57. H. Sakamoto, M. Mori, M. Taira, T. Yoshida, S. Matsukawa, K. Shimizu, M. Sekiguchi, M. Terada, and T. Sugimura, 1986, Transforming gene from human stomach cancers and a non-cancerous portion of stomach mucosa, Proc. Natl. Acad. Sci. USA 83:3997–4001.PubMedCrossRefGoogle Scholar
  58. A. L. Schechter, D. F. Stern, L. Valdyanathan, S. J. Decker, J. A. Drebin, M. E. Greene, and R. A. Weinberg, 1984, The neu oncogene: an erb B related gene encoding a 185,000-M tumor antigen, Nature 312:513–516.PubMedCrossRefGoogle Scholar
  59. C. A. Schoenenberger, A. C. Andres, B. Groner, M. van der Valk, M. LeMeur, and P. Gerlinger, 1988, Targeted c-myc gene expression in mammary glands of transgenic mice induces mammary tumors with constitutive milk protein gene transcription, EMBO J. 7:169–179.PubMedGoogle Scholar
  60. G. M. Shackleford and H. Varmus, 1987, Expression of the proto-oncogene int-1 is restricted to postmeiotic male germ cells and the neural tube of mid-gestational embryos, Cell 50:89–100.PubMedCrossRefGoogle Scholar
  61. C. Shih, L. Padney, M. Murray, and R. A. Weinberg, 1981, Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts, Nature 290:261–264.PubMedCrossRefGoogle Scholar
  62. E. Sinn, W. Muller, P. Pattengale, I. Tepler, R. Wallace, and P. Leder, 1987, Coexpression of MMTV/v-H-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo, Cell 49:465–475.PubMedCrossRefGoogle Scholar
  63. D. J. Slamon, G. M. Clark, S. G. Wong, W. S. Levin, A. Ullrich, and W. L. McGuire, 1987, Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene, Science 235:177–182.PubMedCrossRefGoogle Scholar
  64. E. J. Stanbridge, R. R. Flandermeyer, D. W. Daniels, and W. A. Nelson-Rees, 1981, Specific chromosome loss associated with the expression of tumorigenicity in human cell hybrids, Somatic Cell Genet. 7:699–712.PubMedCrossRefGoogle Scholar
  65. T. Stewart, P. Pattengale, and P. Leder, 1984, Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MMTV/myc fusion genes. Cell 38:627–637.PubMedCrossRefGoogle Scholar
  66. N. Teich, J. Wyke, T. Mak, A. Bernstein, and W. Hardy, 1982, Pathogenesis of retrovirus induced disease, in: “Molecular Biology of Tumor Viruses, RNA Tumor Viruses,” R. Weiss, N. Teich, H. E. Varmus, and J. Coffin, eds., Cold Spring Harbor Laboratory, New York.Google Scholar
  67. Y. Tsujimoto, J. Yunis, L. Onorato-Shouie, J. Erikson, P. C. Nowell, and C. M. Croce, 1984, Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation, Science 224:1403–1406.PubMedCrossRefGoogle Scholar
  68. M. van de Vijver, R. van de Bersselaar, P. Devilee, C. Cornelisse, J. Peterse, and R. Nusse, 1987, Amplification of neu (c-erb B-2) oncogene in human mammary tumors is relatively frequent and is often accompanied by amplification of the linked c-erb A oncogene, Mol. Cell Biol. 7:2019–2023.PubMedGoogle Scholar
  69. M. J. van de Vijver, J. L. Peterse, W. J. Mooi, P. Wisman, J. Lomans, and R. Nusse, 1988, Overexpression of the neu (or c-erb B-2 or HER-2) protein is very frequent in comedo type ductal carcinoma in situ but not of prognostic value in stage II breast cancer, N. Engl. J. Med. 319:1239–1245.PubMedCrossRefGoogle Scholar
  70. A. van Ooyen and R. Nusse, 1984, Structure and nucleotide sequence of the putative mammary oncogene int-1: proviral insertions leave the protein-encoding domain intact, Cell 39:233–240.PubMedCrossRefGoogle Scholar
  71. J. M. Varley, J. E. Swallow, W. J. Brammar, J. L. Whittaker, and R. A. Walker, 1987, Alterations to either c-erb B-2 (neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis, Oncogene 1:423–430.PubMedGoogle Scholar
  72. J. M. Varley, R. A. Walker, G. Casey, and W. J. Brammar, 1988, A common alteration to the int-2 proto-oncogene in DNA from primary breast carcinomas, Oncogene 3:87–90.Google Scholar
  73. H. E. Varmus, 1982, Recent evidence for oncogenesis by insertion mutagenesis and gene activation, Cancer Surv. 1:309–319.Google Scholar
  74. D. J. Venter, N. L. Tuzi, S. Kumar, and W. J. Gullick, 1987, Overexpression of the c-erb B-2 oncoprotein in human breast carcinomas: immunohistological assessment correlates with gene amplification, Lancet ii:69–72.CrossRefGoogle Scholar
  75. C. Weinberger, C. C. Thompson, E. S. Ong, R. Lebo, D. J. Gruol, and R. M. Evans, 1986, The c-erb A gene encodes a thyroid hormone receptor, Nature 324:641–646.PubMedCrossRefGoogle Scholar
  76. R. N. Weiss, N. Teich, H. Varmus, and J. Coffin, 1982, Origins of contemporary RNA tumor virus research, in: “Molecular Biology of Tumor Viruses, RNA Tumor Viruses,” R. Weiss, N. Teich, H. Varmus, and J. Coffin, eds., Cold Spring Harbor Laboratory, New York.Google Scholar
  77. C. W. Welsch, 1985, Host factors affecting the growth of carcinogen-induced rat mammary carcinomas: a review and tribute to Charles Brenton Huggins, Cancer Res. 45:3415–3443.PubMedGoogle Scholar
  78. D. G. Wilkinson, J. A. Bailes, and A. P. McMahon, 1987, Expression of the proto-oncogene int-1 is restricted to specific neural cells in the developing mouse embryo, Cell 50:79–89.PubMedCrossRefGoogle Scholar
  79. T. Yoshida, K. Miyagawa, H. Odagiri, H. Sakamoto, P. F. R. Little, M. Terada, and T. Sugimura, 1987, Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2 encoded protein, Proc. Natl. Acad. Sci. USA 84:7305–7309.PubMedCrossRefGoogle Scholar
  80. J. J. Yunis and A. L. Soreng, 1984, Constitutional fragile sites and cancer, Science 226:1199–1204.PubMedCrossRefGoogle Scholar
  81. D. Zhou, H. Battifora, J. Yokota, T. Yamamoto, and M. J. Cline, 1987, Association of multiple copies of the c-erb B-2 oncogene with spread of breast cancer, Cancer Res. 47:6123–6125.PubMedGoogle Scholar
  82. D. J. Zhou, G. Casey, and M. J. Cline, 1988, Amplification of human int-2 in breast cancers and squamous carcinomas, Oncogene 2:279–282.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Robert Callahan
    • 1
  1. 1.Laboratory of Tumor Immunology and Biology, National Cancer InstituteNational Institutes of HealthBethesdaUSA

Personalised recommendations