Nature Publishing Group, publisher of Nature, and other science journals and reference works
Nature
my account e-alerts subscribe register
   
Sunday 25 June 2017
Journal Home
Current Issue
AOP
Archive
Download PDF
References
Export citation
Export references
Send to a friend
More articles like this

Article
Nature 386, 796 - 804 (24 April 1997); doi:10.1038/386796a0

Phenotype of mice lacking functional Deleted in colorectal cancer (Dec) gene

Amin Fazeli*, Stephanie L. Dickinson*, Michelle L. Hermiston, Robert V. Tighe*, Robert G. Steen, Clayton G. Small*, Esther T. Stoeckli§, Kazuko Keino-Masu§, Masayuki Masu§, Helen Rayburn, Jonathan Simons£, Roderick T. Bronsonstar, Jeffrey I. Gordon, Marc Tessier-Lavigne§ & Robert A. Weinberg*

*Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
Massachusetts Institute of Technology/Whitehead Institute Genome Center, Cambridge, Massachusetts 02142, USA
§Howard Hughes Medical Institute and Department of Anatomy, Programs in Cell Biology, Developmental Biology and Neuroscience, University of California, San Francisco, California 94143, USA
National Defense Medical College, Department of Physiology, Saitama, 359, Japan
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
£Brady Urological Institute, Johns Hopkins University, Baltimore, Maryland 21207, USA
starDepartment of Pathology, Tufts University Schools of Medicine and Veterinary Medicine, Boston, Massachusetts 02111, USA

The DCC (Deleted in colorectal cancer) gene was first identified as a candidate for a tumour-suppressor gene on human chromosome 18q. More recently, in vitro studies in rodents have provided evidence that DCC might function as a receptor for the axonal chemoattractant netrin-1. Inactivation of the murine Dcc gene caused defects in axonal projections that are similar to those observed in netrin-1-deficient mice but did not affect growth, differentiation, morphogenesis or tumorigenesis in mouse intestine. These observations fail to support a tumour-suppressor function for Dcc, but are consistent with the hypothesis that DCC is a component of a receptor for netrin-1.

  1. Fearon, E. R. et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247, 49−56 (1990). | PubMed | ISI | ChemPort |
  2. Cavenee, W. K. et al. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305, 779−784 (1983). | Article | PubMed | ISI | ChemPort |
  3. Boland, C. R., Sato, J., Appelman, H. D., Bresalier, R. S. & Feinberg, A. P. Microallelotyping defines the sequence and tempo of allelic losses at tumour suppressor gene loci during colorectal cancer progression. Nature Med. 1, 902−909 (1995). | Article | PubMed | ISI | ChemPort |
  4. Vogelstein, B. et al. Genetic alterations during colorectal-tumor development. N. Engl. J. Med. 319, 525−532 (1988). | PubMed | ISI | ChemPort |
  5. Tanaka, K. et al. Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18. Nature 349, 340−342 (1991). | Article | PubMed | ISI | ChemPort |
  6. Goyette, M. C. et al. Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer. Mol. Cell. Biol. 12, 1387−1395 (1992). | PubMed | ISI | ChemPort |
  7. Cho, K. R. et al. The DCC gene: structural analysis and mutations in colorectal carcinomas. Genomics 19, 525−531 (1994). | Article | PubMed | ISI | ChemPort |
  8. Kikuchi-Yanoshita, R., Konishi, M., Fukunari, H., Tanaka, K. & Miyaki, M. Loss of expression of the DCC gene during progression of colorectal carcinomas in familial adenomatous polyposis and non-familial adenomatous polyposis patients. Cancer Res. 52, 3801−3803 (1992). | PubMed | ChemPort |
  9. Thiagalingam, S. et al. Evaluation of candidate tumor suppressor genes on chromosome 18 in colorectal cancers. Nature Genet. 13, 343−346 (1996). | Article | PubMed | ISI | ChemPort |
  10. Narayanan, R. et al. Antisense RNA to the putative tumor-suppressor gene DCC transforms Rat-1 fibroblasts. Oncogene 7, 553−561 (1992). | PubMed | ISI | ChemPort |
  11. Klingelhutz, A. J., Hedrick, L., Cho, K. R. & McDougall, J. K. The DCC gene suppresses the malignant phenotype of transformed human epithelial cells. Oncogene 10, 1581−1586 (1995). | PubMed | ISI | ChemPort |
  12. Keino-Masu, K. et al. Deleted in colon cancer (DCC) encodes a netrin receptor. Cell 87, 175−185 (1996). | Article | PubMed | ChemPort |
  13. Tessier-Lavigne, M., Placzek, M., Lumsden, A. G. S., Dodd, J. & Jessell, T. M. Chemotropic guidance of developing axons in the mammalian central nervous system. Nature 336, 775−778 (1988). | Article | PubMed | ChemPort |
  14. Placzek, M., Tessier-Lavigne, M., Jessell, T. M. & Dodd, J. Orientation of commissural axons in vitro in response to a floor plate-derived chemoattractant. Development 110, 19−30 (1990). | PubMed | ISI | ChemPort |
  15. Serafini, T. et al. The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell 78, 409−424 (1994). | Article | PubMed | ISI | ChemPort |
  16. Kennedy, T. E., Serafini, T., de la Torre, J. R. & Tessier-Lavigne, M. Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. Cell 78, 425−435 (1994). | Article | PubMed | ISI | ChemPort |
  17. Serafini, T. et al. Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system. Cell 87, 1001−1014 (1996). | Article | PubMed | ISI | ChemPort |
  18. Ishii, N., Wadsworth, W. G., Stern, B. D., Culotti, J. G. & Hedgecock, E. M. UNC-6, a laminin-related protein, guides cell and pioneer axon migrations in C. elegans. Neuron 9, 873−881 (1992). | Article | PubMed | ISI | ChemPort |
  19. Wadsworth, W. G., Bhatt, H. & Hedgecock, E. M. Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin cues for guiding migrations in C. elegans. Neuron 16, 35−46 (1996). | Article | PubMed | ISI | ChemPort |
  20. Mitchell, K. J. et al. Genetic analysis of Netrin genes in Drosophila: netrins guide CNS commissural axons and peripheral motor axons. Neuron 17, 203−215 (1996). | Article | PubMed | ISI | ChemPort |
  21. Harris, R., Sabatelli, L. M. & Seeger, M. A. Guidance cues at the drosophila CNS midline: identification and characterization of two Drosophila Netrin/UNC-6 homologs. Neuron 17, 217−228 (1996). | Article | PubMed | ISI | ChemPort |
  22. Chan, S. S.-Y. et al. UNC-40, a C. elegans homolog of DCC (deleted in colorectal cancer), is required in motile cells responding to UNC-6 netrin cues. Cell 87, 187−195 (1996). | Article | PubMed | ISI | ChemPort |
  23. Kolodziej, P. A. et al. frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance. Cell 87, 197−204 (1996). | Article | PubMed | ISI | ChemPort |
  24. Gossler, A., Doetschman, T., Korn, R., Serfling, E. & Kemler, R. Transgenesis by means of blastocyst-derived embryonic stem cell lines. Proc. Natl Acad. Sci. USA 83, 9065−9069 (1986). | PubMed | ChemPort |
  25. Fearon, E. R. & Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61, 759−767 (1990). | Article | PubMed | ISI | ChemPort |
  26. Fearon, E. in The Molecular Basis of Cancer (ed. Mendelsohn, J.) 340−355 (Saunders, Philadelphia, 1995).
  27. Moser, A. R., Pitot, H. C. & Dove, W. F. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247, 322−324 (1990). | PubMed | ISI | ChemPort |
  28. Su, L. K. et al. Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science 256, 668−670 (1992). | PubMed | ISI | ChemPort |
  29. Moser, A. R., Dove, W. F., Roth, K. A. & Gordon, J. I. The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system. J. Cell Biol. 116, 1517−1526 (1992). | Article | PubMed | ISI | ChemPort |
  30. Justice, M. J. et al. A molecular genetic linkage map of mouse chromosome 18 reveals extensive linkage conservation with human chromosomes 5 and 18. Genomics 13, 1281−1288 (1992). | Article | PubMed | ISI | ChemPort |
  31. Luongo, C. et al. Mapping of multiple intestinal neoplasia (Min) to proximal chromosome 18 of the mouse. Genomics 15, 3−8 (1993). | Article | PubMed | ISI | ChemPort |
  32. Luongo, C., Moser, A. R., Gledhill, S. & Dove, W. F. Loss of Apc+ in intestinal adenomas from Min mice. Cancer Res. 54, 5947−5952 (1994). | PubMed | ISI | ChemPort |
  33. Levy, D. B. et al. Inactivation of both APC alleles in human and mouse tumors. Cancer Res. 54, 5953−5458 (1994). | PubMed | ISI | ChemPort |
  34. Laird, P. W. et al. Suppression of intestinal neoplasia by DNA hypomethylation. Cell 81, 197−205 (1995). | Article | PubMed | ISI | ChemPort |
  35. Chandrasekaran, C. & Grodon, J. I. Cell lineage-specific and differentiation-dependent patterns of CCAAT/enhancer binding protein alpha expression in the gut epithelium of normal and transgenic mice. Proc. Natl Acad. Sci. USA 90, 8871−8875 (1993). | PubMed | ChemPort |
  36. Falk, P., Roth, K. A. & Gordon, J. I. Lectins are sensitive tools for defining the differentiation programs of mouse gut epithelial cell lineages. Am. J. Physiol. 266, G987−1003 (1994). | PubMed | ChemPort |
  37. Roth, K. A. & Gordon, J. I. Spatial differentiation of the intestinal epithelium: analysis of enteroendocrine cells containing immunoreactive serotonin, secretin, and substance P in normal and transgenic mice. Proc. Natl Acad. Sci. USA 87, 6408−6412 (1990). | PubMed | ChemPort |
  38. Hedrick, L. et al. The DCC gene product in cellular differentiation and colorectal tumorigenesis. Genes Dev. 8, 1174−1183 (1994). | PubMed | ChemPort |
  39. Bry, L. et al. Paneth cell differentiation in the developing intestine of normal and transgenic mice. Proc. Natl Acad. Sci. USA 91, 10335−10339 (1994). | PubMed | ChemPort |
  40. Louvard, D., Kedinger, M. & Hauri, H. P. The differentiating intestinal epithelial cell: establishment and maintenance of functions through interactions between cellular structures. Annu. Rev. Cell Biol. 8, 157−195 (1992). | Article | PubMed | ISI | ChemPort |
  41. Schmidt, G. H., Winton, D. J. & Ponder, B. A. Development of the pattern of cell renewal in the crypt-villus unit of chimaeric mouse small intestine. Development 103, 785−790 (1988). | PubMed | ISI | ChemPort |
  42. Hermiston, M. L., Green, R. P. & Gordon, J. I. Chimeric-transgenic mice represent a powerful tool for studying how the proliferation and differentiation programs of intestinal epithelial cell lineages are regulated. Proc. Natl Acad. Sci. USA 90, 8866−8870 (1993). | PubMed | ChemPort |
  43. Hermiston, M. L. & Gordon, J. I. In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death. J. Cell Biol. 129, 489−506 (1995). | Article | PubMed | ISI | ChemPort |
  44. Dodd, J., Morton, S. B., Karagogeos, D., Yamamoto, M. & Jessell, T. M. Spatial regulation of axonal glycoprotein expression on subsets of embryonic spinal neurons. Neuron 1, 105−116 (1988). | Article | PubMed | ISI | ChemPort |
  45. Hohne, M. W., Halatsch, M. E., Kahl, G. F. & Weinel, R. J. Frequent loss of expression of the potential tumor suppressor gene DCC in ductal pancreatic adenocarcinoma. Cancer Res. 52, 2616−2619 (1992). | PubMed | ISI | ChemPort |
  46. Hahn, S. A. et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 271, 350−353 (1996). | PubMed | ISI | ChemPort |
  47. Goodman, C. S. The likeness of being: phylogenetically conserved molecular mechanisms of growth cone guidance. Cell 78, 353−356 (1994). | Article | PubMed | ISI | ChemPort |
  48. Mortensen, R. M., Conner, D. A., Chao, S., Geisterfer-Lowrance, A. A. & Seidman, J. G. Production of homozygous mutant ES cells with a single targeting construct. Mol. Cell. Biol. 12, 2391−2395 (1992). | PubMed | ISI | ChemPort |
  49. Stoeckli, E. T. & Landmesser, L. T. Axonin-1, Nr-CAM, and Ng-CAM play different roles in the in vivo guidance of chick commissural neurons. Neuron 14, 1165−1179 (1995). | Article | PubMed | ISI | ChemPort |
  50. Ekstrand, B. C., Mansfield, T. A., Bigner, S. H. & Fearon, E. R. Dcc expression is altered by multiple mechanisms in brain tumors. Oncogene 11, 2393−2402 (1995). | PubMed | ISI | ChemPort |



© 1997 Nature Publishing Group
Privacy Policy