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H–cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer

Nature Medicine volume 2, pages 776–782 (1996)Cite this article

Abstract

A newly identified gene, H–cadherin, is reported. H–cadherin encodes a protein related to the cadherin superfamily of cell adhesion molecules, and its expression is shown to be significantly reduced in human breast carcinoma cell lines and breast cancer specimens. H–cadherin was localized to chromosome 16q24 and is highly expressed in the heart. Introduction of H–cadherin cDNA markedly diminished tumor cell growth and resulted in a significant change from invasive morphology to a normal cell–like morphology in the Matrigel outgrowth assay. These studies indicate that downregulation of H–cadherin may be frequent in the breast malignant progression and suggest that it may have prognostic value as a marker for breast cancer development.

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References

  1. Weinberg, R.A. Tumor suppressor genes. Science 254, 1138–1146 (1991).

    Article  CAS  PubMed  Google Scholar 

  2. Bishop, J.M., Cancer: The rise of the genetic paradigm. Genes Dev. 9, 1309–1315 (1995).

    Article  CAS  PubMed  Google Scholar 

  3. Sainbury, J.R.C., Farndon, J.R., Needham, G.K., Malcolm, A.J. & Harris, A.L. Epidermal growth factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 1, 1398–1402 (1987).

    Google Scholar 

  4. Slamon, D.J. et al. Human breast cancer: Correlation of relapse and survival with amplification of the Her2/neu oncogene. Science 235, 177–182 (1987).

    Article  CAS  PubMed  Google Scholar 

  5. Katsumata, M. et al. Prevention of breast tumor development in vivo by down-regulation of the p185neu receptor. Nature Med. 1, 644–648 (1995).

    Article  CAS  PubMed  Google Scholar 

  6. Friend, S.H. et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323, 643–646 (1986).

    Article  CAS  PubMed  Google Scholar 

  7. Levine, A.J., Momand, J. & Finlay, C.A. The p53 tumor suppressor gene. Nature 351, 453–456 (1991).

    Article  CAS  PubMed  Google Scholar 

  8. Fearon, E.R. et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247, 49–56 (1990).

    Article  CAS  PubMed  Google Scholar 

  9. Powell, S.M. et al. APC mutations occur early during colorectal tumorigenesis. Nature 359, 235–237 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Pritchard-Jones, K. et al. The candidate Wilms's tumor gene is involved in genitourinary development. Nature 346, 194–197 (1990).

    Article  CAS  PubMed  Google Scholar 

  11. Liotta, L.A., Stetler-Stevenson, W.G. & Steeg, P.S. Metastasis suppressor genes. Important Adv. Oncol. 85–100 (1991).

  12. El-Deiry, W.S. et al. WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817–825 (1993).

    Article  CAS  PubMed  Google Scholar 

  13. Malkin, D. et al. Germ line p53 mutations in familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250, 1233–1238 (1990).

    Article  CAS  PubMed  Google Scholar 

  14. Miki, Y. et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266, 66–71 (1994).

    Article  CAS  PubMed  Google Scholar 

  15. Holt, J.T. et al. Growth retardation and tumour inhibition by BRCA1. Nature Genet. 12, 298–302 (1996).

    Article  CAS  PubMed  Google Scholar 

  16. Jensen, R.A. et al. BRAC1 is secreted and exhibits properties of a granin. Nature Genet. 12, 303–308 (1996).

    Article  CAS  PubMed  Google Scholar 

  17. Takeichi, M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 251, 1451–1455 (1991).

    Article  CAS  PubMed  Google Scholar 

  18. Takeichi, M. Cadherins in cancer: Implications for invasion and metastasis. Curr. Opin. Cell Biol. 5, 806–811 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Behrens, J. The role of adhesion molecules in cancer invasion and metastasis. Breast Cancer Res. Treat. 24, 175–184 (1993).

    Article  CAS  PubMed  Google Scholar 

  20. Mayer, B. et al. E-cadherin expression in primary and metastatic gastric cancer: Down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res. 53, 1690–1695 (1993).

    CAS  PubMed  Google Scholar 

  21. Bringuier, P.P. et al. Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res. 53, 3241–3245 (1993).

    CAS  PubMed  Google Scholar 

  22. Oka, H. et al. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 53, 1696–1701 (1993).

    CAS  PubMed  Google Scholar 

  23. Mahoney, P.A. et al. The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily. Cell 67, 853–868 (1991).

    Article  CAS  PubMed  Google Scholar 

  24. Matsuzaki, F. et al. cDNAs of cell adhesion molecules of different specificity induce changes in cell shape and border formation in cultured S180 cells. J. Cell Biol. 110, 1239–1252 (1990).

    Article  CAS  PubMed  Google Scholar 

  25. Shapiro, L. et al. Structural basis of cell–cell adhesion by cadherins. Nature 374, 327–337 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. Solomon, E., Borrow, J. & Goddard, A.D. Chromosome aberrations and cancer. Nature 254, 1153–1160 (1991).

    CAS  Google Scholar 

  27. Sato, T., Akiyama, F., Sakamoto, G., Kasumi, F. & Nakamura, Y. Accumulation of genetic alterations and progression of primary breast cancer. Cancer Res. 51, 5794–5799 (1991).

    CAS  PubMed  Google Scholar 

  28. Lindblom, A., Rotstein, S., Skoog, L., NordenskjØld, M. & Larsson, C. Deletions on chromosome 16 in primary familial breast carcinomas are associated with development of distant metastases. Cancer Res. 53, 3707–3711 (1993).

    CAS  PubMed  Google Scholar 

  29. Tsuda, H. & Horohashi, S. Identification of multiple breast cancers of multicentric origin by histological observations and distribution of allele loss on chromosome 16q. Cancer Res. 55, 3395–3398 (1995).

    CAS  PubMed  Google Scholar 

  30. Tsuda, H., Callen, D.F., Fukutomi, T., Nakamura, Y. & Horohashi, S. Allele loss on chromosome 16q24.2-qter occurs frequently in breast cancers irrespectively of differences in phenotype and extent of spread. Cancer Res. 54, 513–517 (1994).

    CAS  PubMed  Google Scholar 

  31. Lee, S.W., Tomasetto, C. & Sager, R. Positive selection of candidate tumor suppressor genes by subtractive hybridization. Proc. Natl. Acad. Sci. USA 88, 2825–2829 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Carter, B.S. et al. Allelic loss of chromosomes 16q and 10q in human prostate cancer. Proc. Natl. Acad. Sci. USA 87, 8751–8755 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tsuda, H., Oda, T., Sakamoto, M. & Hirohashi, S. Different pattern of chromosomal allele loss in multiple hepatocellular carcinomas as evidence of their multifocal origin. Cancer Res. 52, 1504–1509 (1992).

    CAS  PubMed  Google Scholar 

  34. Vleminckx, K., Vakaet, L., Mareel, M., Fiers, W. & van Roy, F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 66, 107–119 (1991).

    Article  CAS  PubMed  Google Scholar 

  35. Watabe, M., Nagafuchi, A., Tsukita, S. & Takeichi, M. Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line. J. Cell Biol. 127, 247–256 (1994).

    Article  CAS  PubMed  Google Scholar 

  36. Hermiston, M.L. & Gordon, J.I. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science 270, 1203–1207 (1995).

    Article  CAS  PubMed  Google Scholar 

  37. Hendrix, M.J., Seftor, E.A., Seftor, R.E.B. & Fidler, I.J. Simple quantitative assay for studying the invasive potential of high and low human metastatic variants. Cancer Lett. 38, 137–147 (1987).

    Article  CAS  PubMed  Google Scholar 

  38. Kinsella, A.R. et al. The role of the cell-cell adhesion molecule E-cadherin in large bowel tumour cell invasion and metastasis. Br. J. Cancer 67, 804–809 (1992).

    Google Scholar 

  39. Bongiorno, P.F. et al. E-cadherin expression in primary and metastatic thoracic neoplasms and in Barrett's esophagus. Br. J. Cancer 71, 166–172 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Navarro, P., Lozano, E. & Cano, E. Expression of E-or P-cadherin is not sufficient to modify the morphology and the tumorigenic behavior of murine spindle carcinoma cells: Possible involvement of plakoglobin. J. Cell Sci. 105, 923–934 (1993).

    CAS  PubMed  Google Scholar 

  41. Sommers, C.L., Gelmann, E.P., Kemler, R., Cowin, P. & Byers, S.W. Alterations of β-catenin phosphorylation and plakoglobin expression in human breast cancer cells. Cancer Res. 54, 3544–3552 (1994).

    CAS  PubMed  Google Scholar 

  42. Simcha, I., Geiger, B., Yehuda-levenberg, S., Salomon, D. & Ben-Ze'ev, A. Suppression of tumorigenicity by plakoglobin: An augmenting effect of N-cadherin. J. Cell Biol. 133, 199–209 (1996).

    Article  CAS  PubMed  Google Scholar 

  43. Ranscht, B. & Dours-Zimmermann, M.T., T-cadherin, a novel cadherin cell adhesion molecule in the nervous system lacks the conserved cytoplasmic region. Neuron 7, 391–402 (1991).

    Article  CAS  PubMed  Google Scholar 

  44. Dantzig, A.H. et al. Association of intestinal peptide transport with a protein related to the cadherin superfamily. Science 264, 430–433 (1994).

    Article  CAS  PubMed  Google Scholar 

  45. Thomson, R.B. et al. Isolation and cDNA cloning of Ksp-cadherin, a novel kidney-specific member of the cadherin multigene family. J. Biol. Chem. 270, 17594–17601 (1995).

    Article  CAS  PubMed  Google Scholar 

  46. Berndorff, D. et al. Liver-intestine cadherin: Molecular cloning and characterization of a novel Ca2+)-dependent cell adhesion molecule expressed in liver and intestine. J. Cell Biol. 125, 1353–1369 (1994).

    Article  CAS  PubMed  Google Scholar 

  47. Stappert, J. & Kemler, R. Intracellular association of adhesion molecules. Curr. Opin. Neurobiol. 3, 60–66 (1993).

    Article  CAS  PubMed  Google Scholar 

  48. Su, L-K., Vogelstein, B. & Kinzler, K.W. Association of the APC tumor suppressor protein with catenin. Science 262, 1734–1737 (1993).

    Article  CAS  PubMed  Google Scholar 

  49. Rubinfeld, B. et al. Association of the APC gene product with β-catenin. Science 262, 1731–1733 (1993).

    Article  CAS  PubMed  Google Scholar 

  50. Nagafuchi, A., Tsukita, S. & Takeichi, M. Transmembrane control of cadherin-mediated cell-cell adhesion. Semin. Cell Biol. 4, 175–181 (1993).

    Article  CAS  PubMed  Google Scholar 

  51. Band, V. & Sager, R. Distinctive traits of normal and tumor derived human mammary epithelial cells expressed in a medium that supports long-term growth of both cell types. Proc. Natl. Acad. Sci. USA 86, 1249–1253 (1990).

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Beth Israel Hospital,

    Sam W. Lee

  2. Division on Aging, Harvard Medical School,

    Sam W. Lee

  3. Harvard Institutes of Medicine, Room 921, 77 Avenue Louis Pasteur, Boston, Massachusetts, 02215, USA

    Sam W. Lee

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  1. Sam W. Lee
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Lee, S. H–cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer. Nat Med 2, 776–782 (1996). https://doi.org/10.1038/nm0796-776

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