Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Jan;148(1):39–46.

Beta-catenin expression in human cancers.

T Takayama 1, H Shiozaki 1, S Shibamoto 1, H Oka 1, Y Kimura 1, S Tamura 1, M Inoue 1, T Monden 1, F Ito 1, M Monden 1
PMCID: PMC1861624  PMID: 8546224

Abstract

Cell-cell adhesion in tissue is mainly regulated by homotypic interaction of cadherin molecules, which are anchored to the cytoskeleton via cytoplasmic proteins, including alpha- and beta-catenin. Although we previously demonstrated that alpha-catenin is crucial for cadherin function in vivo, little is known about the role of beta-catenin. We examined the expression of beta-catenin in human carcinoma samples along with normal tissue (esophagus, stomach, and colon) by immunostaining using our antibody for beta-catenin. Normal epithelium strongly expressed beta-catenin. However, beta-catenin expression was frequently reduced in primary tumors of the esophagus (10 of 15, 67%), stomach (9 of 19, 47%), and colon (11 of 22, 50%). From an immunoprecipitation study, we found that beta-catenin forms a complex with E-cadherin not only in the normal epithelium but also in cancerous tissues. In coexpression patterns of E-cadherin and beta-catenin, 43 (77%) of the 56 tumors showed a similar expression of both molecules, whereas the other 13 tumors (23%) showed positive staining for E-cadherin and reduced expression of beta-catenin. These findings suggest that beta-catenin forms a complex with E-cadherin in vivo and down-regulation of beta-catenin expression is associated with malignant transformation.

Full text

PDF
39

Images in this article

42Figure 1
on p.42
43Figure 2
on p.43
44Figure 3
on p.44

Selected References

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

  1. Aberle H., Butz S., Stappert J., Weissig H., Kemler R., Hoschuetzky H. Assembly of the cadherin-catenin complex in vitro with recombinant proteins. J Cell Sci. 1994 Dec;107(Pt 12):3655–3663. doi: 10.1242/jcs.107.12.3655. [DOI] [PubMed] [Google Scholar]
  2. Becker K. F., Atkinson M. J., Reich U., Becker I., Nekarda H., Siewert J. R., Höfler H. E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. 1994 Jul 15;54(14):3845–3852. [PubMed] [Google Scholar]
  3. Behrens J., Vakaet L., Friis R., Winterhager E., Van Roy F., Mareel M. M., Birchmeier W. Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J Cell Biol. 1993 Feb;120(3):757–766. doi: 10.1083/jcb.120.3.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hamaguchi M., Matsuyoshi N., Ohnishi Y., Gotoh B., Takeichi M., Nagai Y. p60v-src causes tyrosine phosphorylation and inactivation of the N-cadherin-catenin cell adhesion system. EMBO J. 1993 Jan;12(1):307–314. doi: 10.1002/j.1460-2075.1993.tb05658.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hoschuetzky H., Aberle H., Kemler R. Beta-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor. J Cell Biol. 1994 Dec;127(5):1375–1380. doi: 10.1083/jcb.127.5.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  7. Inoue M., Ogawa H., Miyata M., Shiozaki H., Tanizawa O. Expression of E-cadherin in normal, benign, and malignant tissues of female genital organs. Am J Clin Pathol. 1992 Jul;98(1):76–80. doi: 10.1093/ajcp/98.1.76. [DOI] [PubMed] [Google Scholar]
  8. Kadowaki T., Shiozaki H., Inoue M., Tamura S., Oka H., Doki Y., Iihara K., Matsui S., Iwazawa T., Nagafuchi A. E-cadherin and alpha-catenin expression in human esophageal cancer. Cancer Res. 1994 Jan 1;54(1):291–296. [PubMed] [Google Scholar]
  9. Matsui S., Shiozaki H., Inoue M., Tamura S., Doki Y., Kadowaki T., Iwazawa T., Shimaya K., Nagafuchi A., Tsukita S. Immunohistochemical evaluation of alpha-catenin expression in human gastric cancer. Virchows Arch. 1994;424(4):375–381. doi: 10.1007/BF00190559. [DOI] [PubMed] [Google Scholar]
  10. Matsuyoshi N., Hamaguchi M., Taniguchi S., Nagafuchi A., Tsukita S., Takeichi M. Cadherin-mediated cell-cell adhesion is perturbed by v-src tyrosine phosphorylation in metastatic fibroblasts. J Cell Biol. 1992 Aug;118(3):703–714. doi: 10.1083/jcb.118.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McCrea P. D., Brieher W. M., Gumbiner B. M. Induction of a secondary body axis in Xenopus by antibodies to beta-catenin. J Cell Biol. 1993 Oct;123(2):477–484. doi: 10.1083/jcb.123.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McCrea P. D., Turck C. W., Gumbiner B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science. 1991 Nov 29;254(5036):1359–1361. doi: 10.1126/science.1962194. [DOI] [PubMed] [Google Scholar]
  13. Nagafuchi A., Takeichi M., Tsukita S. The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. Cell. 1991 May 31;65(5):849–857. doi: 10.1016/0092-8674(91)90392-c. [DOI] [PubMed] [Google Scholar]
  14. Oda T., Kanai Y., Oyama T., Yoshiura K., Shimoyama Y., Birchmeier W., Sugimura T., Hirohashi S. E-cadherin gene mutations in human gastric carcinoma cell lines. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1858–1862. doi: 10.1073/pnas.91.5.1858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Oka H., Shiozaki H., Kobayashi K., Inoue M., Tahara H., Kobayashi T., Takatsuka Y., Matsuyoshi N., Hirano S., Takeichi M. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 1993 Apr 1;53(7):1696–1701. [PubMed] [Google Scholar]
  16. Oka H., Shiozaki H., Kobayashi K., Tahara H., Tamura S., Miyata M., Doki Y., Iihara K., Matsuyoshi N., Hirano S. Immunohistochemical evaluation of E-cadherin adhesion molecule expression in human gastric cancer. Virchows Arch A Pathol Anat Histopathol. 1992;421(2):149–156. doi: 10.1007/BF01607048. [DOI] [PubMed] [Google Scholar]
  17. Oyama T., Kanai Y., Ochiai A., Akimoto S., Oda T., Yanagihara K., Nagafuchi A., Tsukita S., Shibamoto S., Ito F. A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines. Cancer Res. 1994 Dec 1;54(23):6282–6287. [PubMed] [Google Scholar]
  18. Ozawa M., Baribault H., Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989 Jun;8(6):1711–1717. doi: 10.1002/j.1460-2075.1989.tb03563.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ozawa M., Kemler R. Molecular organization of the uvomorulin-catenin complex. J Cell Biol. 1992 Feb;116(4):989–996. doi: 10.1083/jcb.116.4.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ozawa M., Ringwald M., Kemler R. Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4246–4250. doi: 10.1073/pnas.87.11.4246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rubinfeld B., Souza B., Albert I., Müller O., Chamberlain S. H., Masiarz F. R., Munemitsu S., Polakis P. Association of the APC gene product with beta-catenin. Science. 1993 Dec 10;262(5140):1731–1734. doi: 10.1126/science.8259518. [DOI] [PubMed] [Google Scholar]
  22. Shibamoto S., Hayakawa M., Takeuchi K., Hori T., Miyazawa K., Kitamura N., Johnson K. R., Wheelock M. J., Matsuyoshi N., Takeichi M. Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes. J Cell Biol. 1995 Mar;128(5):949–957. doi: 10.1083/jcb.128.5.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shibamoto S., Hayakawa M., Takeuchi K., Hori T., Oku N., Miyazawa K., Kitamura N., Takeichi M., Ito F. Tyrosine phosphorylation of beta-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells. Cell Adhes Commun. 1994 Jan;1(4):295–305. doi: 10.3109/15419069409097261. [DOI] [PubMed] [Google Scholar]
  24. Shimoyama Y., Hirohashi S., Hirano S., Noguchi M., Shimosato Y., Takeichi M., Abe O. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res. 1989 Apr 15;49(8):2128–2133. [PubMed] [Google Scholar]
  25. Shimoyama Y., Hirohashi S., Hirano S., Noguchi M., Shimosato Y., Takeichi M., Abe O. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res. 1989 Apr 15;49(8):2128–2133. [PubMed] [Google Scholar]
  26. Shimoyama Y., Nagafuchi A., Fujita S., Gotoh M., Takeichi M., Tsukita S., Hirohashi S. Cadherin dysfunction in a human cancer cell line: possible involvement of loss of alpha-catenin expression in reduced cell-cell adhesiveness. Cancer Res. 1992 Oct 15;52(20):5770–5774. [PubMed] [Google Scholar]
  27. Shiozaki H., Iihara K., Oka H., Kadowaki T., Matsui S., Gofuku J., Inoue M., Nagafuchi A., Tsukita S., Mori T. Immunohistochemical detection of alpha-catenin expression in human cancers. Am J Pathol. 1994 Apr;144(4):667–674. [PMC free article] [PubMed] [Google Scholar]
  28. Shiozaki H., Kadowaki T., Doki Y., Inoue M., Tamura S., Oka H., Iwazawa T., Matsui S., Shimaya K., Takeichi M. Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line. Br J Cancer. 1995 Feb;71(2):250–258. doi: 10.1038/bjc.1995.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shiozaki H., Tahara H., Oka H., Miyata M., Kobayashi K., Tamura S., Iihara K., Doki Y., Hirano S., Takeichi M. Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am J Pathol. 1991 Jul;139(1):17–23. [PMC free article] [PubMed] [Google Scholar]
  30. Su L. K., Vogelstein B., Kinzler K. W. Association of the APC tumor suppressor protein with catenins. Science. 1993 Dec 10;262(5140):1734–1737. doi: 10.1126/science.8259519. [DOI] [PubMed] [Google Scholar]
  31. Takeichi M. Functional correlation between cell adhesive properties and some cell surface proteins. J Cell Biol. 1977 Nov;75(2 Pt 1):464–474. doi: 10.1083/jcb.75.2.464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tsukita S., Tsukita S., Nagafuchi A., Yonemura S. Molecular linkage between cadherins and actin filaments in cell-cell adherens junctions. Curr Opin Cell Biol. 1992 Oct;4(5):834–839. doi: 10.1016/0955-0674(92)90108-o. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES