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. 2000 Apr 27;82(10):1689–1693. doi: 10.1054/bjoc.1999.1112

Nuclear translocation of beta-catenin in colorectal cancer

M Kobayashi 1, T Honma 1, Y Matsuda 1, Y Suzuki 1, R Narisawa 1, Y Ajioka 2, H Asakura 1
PMCID: PMC2374509  PMID: 10817505

Abstract

Post-translational stabilization of beta-catenin through mutation of the adenomatous polyposis coli (APC) gene has been proposed as an early step in colorectal carcinogenesis. Beta-catenin may translocate from the cytoplasm to the nucleus, where it might serve as a transcriptional factor to stimulate tumour formation. We investigated intracellular localization of beta-catenin in sporadic colorectal adenomas and cancers as well as familial adenomatous polyposis (FAP). Nuclear over-expression of beta-catenin was observed in 35% (7/20) of intramucosal cancers and 42% (23/55) of invasive cancers but was not seen in any adenomas from sporadic or FAP cases. Cytoplasmic beta-catenin in adenomas was significantly higher than that of normal mucosa in both sporadic and FAP cases. The cytoplasmic intensity index of cancers was significantly higher than that of sporadic adenomas, but the index was not correlated with nuclear expression in cancers. These findings suggest that nuclear translocation of beta-catenin is involved in development of intramucosal cancer rather than adenoma, independent of APC mutations. Cytoplasmic accumulation of beta-catenin may occur in adenomas, but it remains to be determined whether this is a cause or a consequence of colorectal cancer. © 2000 Cancer Research Campaign

Keywords: beta-catenin, immunohistochemistry, colorectal cancer, familial adenomatous polyposis (FAP)

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Selected References

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  1. Barth A. I., Näthke I. S., Nelson W. J. Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways. Curr Opin Cell Biol. 1997 Oct;9(5):683–690. doi: 10.1016/s0955-0674(97)80122-6. [DOI] [PubMed] [Google Scholar]
  2. Behrens J., von Kries J. P., Kühl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996 Aug 15;382(6592):638–642. doi: 10.1038/382638a0. [DOI] [PubMed] [Google Scholar]
  3. Günther K., Brabletz T., Kraus C., Dworak O., Reymond M. A., Jung A., Hohenberger W., Kirchner T., Köckerling F., Ballhausen W. G. Predictive value of nuclear beta-catenin expression for the occurrence of distant metastases in rectal cancer. Dis Colon Rectum. 1998 Oct;41(10):1256–1261. doi: 10.1007/BF02258226. [DOI] [PubMed] [Google Scholar]
  4. Inomata M., Ochiai A., Akimoto S., Kitano S., Hirohashi S. Alteration of beta-catenin expression in colonic epithelial cells of familial adenomatous polyposis patients. Cancer Res. 1996 May 1;56(9):2213–2217. [PubMed] [Google Scholar]
  5. Iwao K., Nakamori S., Kameyama M., Imaoka S., Kinoshita M., Fukui T., Ishiguro S., Nakamura Y., Miyoshi Y. Activation of the beta-catenin gene by interstitial deletions involving exon 3 in primary colorectal carcinomas without adenomatous polyposis coli mutations. Cancer Res. 1998 Mar 1;58(5):1021–1026. [PubMed] [Google Scholar]
  6. Jen J., Powell S. M., Papadopoulos N., Smith K. J., Hamilton S. R., Vogelstein B., Kinzler K. W. Molecular determinants of dysplasia in colorectal lesions. Cancer Res. 1994 Nov 1;54(21):5523–5526. [PubMed] [Google Scholar]
  7. Kitaeva M. N., Grogan L., Williams J. P., Dimond E., Nakahara K., Hausner P., DeNobile J. W., Soballe P. W., Kirsch I. R. Mutations in beta-catenin are uncommon in colorectal cancer occurring in occasional replication error-positive tumors. Cancer Res. 1997 Oct 15;57(20):4478–4481. [PubMed] [Google Scholar]
  8. Korinek V., Barker N., Morin P. J., van Wichen D., de Weger R., Kinzler K. W., Vogelstein B., Clevers H. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997 Mar 21;275(5307):1784–1787. doi: 10.1126/science.275.5307.1784. [DOI] [PubMed] [Google Scholar]
  9. Miyoshi Y., Nagase H., Ando H., Horii A., Ichii S., Nakatsuru S., Aoki T., Miki Y., Mori T., Nakamura Y. Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene. Hum Mol Genet. 1992 Jul;1(4):229–233. doi: 10.1093/hmg/1.4.229. [DOI] [PubMed] [Google Scholar]
  10. Morin P. J., Sparks A. B., Korinek V., Barker N., Clevers H., Vogelstein B., Kinzler K. W. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997 Mar 21;275(5307):1787–1790. doi: 10.1126/science.275.5307.1787. [DOI] [PubMed] [Google Scholar]
  11. Munemitsu S., Albert I., Souza B., Rubinfeld B., Polakis P. Regulation of intracellular beta-catenin levels by the adenomatous polyposis coli (APC) tumor-suppressor protein. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):3046–3050. doi: 10.1073/pnas.92.7.3046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Müller O., Nimmrich I., Finke U., Friedl W., Hoffmann I. A beta-catenin mutation in a sporadic colorectal tumor of the RER phenotype and absence of beta-catenin germline mutations in FAP patients. Genes Chromosomes Cancer. 1998 May;22(1):37–41. [PubMed] [Google Scholar]
  13. Novak A., Hsu S. C., Leung-Hagesteijn C., Radeva G., Papkoff J., Montesano R., Roskelley C., Grosschedl R., Dedhar S. Cell adhesion and the integrin-linked kinase regulate the LEF-1 and beta-catenin signaling pathways. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4374–4379. doi: 10.1073/pnas.95.8.4374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Näthke I. S., Adams C. L., Polakis P., Sellin J. H., Nelson W. J. The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration. J Cell Biol. 1996 Jul;134(1):165–179. doi: 10.1083/jcb.134.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Samowitz W. S., Powers M. D., Spirio L. N., Nollet F., van Roy F., Slattery M. L. Beta-catenin mutations are more frequent in small colorectal adenomas than in larger adenomas and invasive carcinomas. Cancer Res. 1999 Apr 1;59(7):1442–1444. [PubMed] [Google Scholar]
  16. Schlemper R. J., Itabashi M., Kato Y., Lewin K. J., Riddell R. H., Shimoda T., Sipponen P., Stolte M., Watanabe H. Differences in the diagnostic criteria used by Japanese and Western pathologists to diagnose colorectal carcinoma. Cancer. 1998 Jan 1;82(1):60–69. doi: 10.1002/(sici)1097-0142(19980101)82:1<60::aid-cncr7>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  17. Valizadeh A., Karayiannakis A. J., el-Hariry I., Kmiot W., Pignatelli M. Expression of E-cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120) in colorectal polyps. Am J Pathol. 1997 Jun;150(6):1977–1984. [PMC free article] [PubMed] [Google Scholar]
  18. Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]

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