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. 2001 Jul;85(1):64–68. doi: 10.1054/bjoc.2001.1863

Mutations of the β- and γ-catenin genes are uncommon in human lung, breast, kidney, cervical and ovarian carcinomas

M Ueda 1, R M Gemmill 2, J West 2, R Winn 2, M Sugita 3, N Tanaka 4, M Ueki 1, H A Drabkin 2
PMCID: PMC2363927  PMID: 11437403

Abstract

β-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator in the Wnt signalling pathway. Although recent investigations have been focused on the role of the adenomatous polyposis coli (APC)/ β-catenin/Tcf pathway in human tumorigenesis, there have been very few reports on mutations of the β-catenin gene in a variety of tumour types. Using PCR and single-strand conformational polymorphism analysis, we examined 93 lung, 9 breast, 6 kidney, 19 cervical and 7 ovarian carcinoma cell lines for mutations in exon 3 of the β-catenin gene. In addition, we tested these same samples for mutations in the NH2-terminal regulatory region of the γ-catenin gene. Mutational analysis for the entire coding region of β-catenin cDNA was also undertaken in 20 lung, 9 breast, 5 kidney and 6 cervical carcinoma cell lines. Deletion of most β-catenin coding exons was confirmed in line NCI-H28 (lung mesothelioma) and a silent mutation at codon 214 in exon 5 was found in HeLa (cervical adenocarcinoma). A missense mutation at codon 19 and a silent mutation at codon 28 in the NH2-terminal regulatory region of the γ-catenin gene were found in H1726 (squamous cell lung carcinoma) and H1048 (small cell lung carcinoma), respectively. Neither deletions nor mutations of these genes were detected in the other cell lines examined. These results suggest that β- and γ-catenins are infrequent mutational targets during development of human lung, breast, kidney, cervical and ovarian carcinomas. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: β-catenin, γ-catenin, gene mutation, human carcinoma

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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. Calvo R., West J., Franklin W., Erickson P., Bemis L., Li E., Helfrich B., Bunn P., Roche J., Brambilla E. Altered HOX and WNT7A expression in human lung cancer. Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12776–12781. doi: 10.1073/pnas.97.23.12776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Candidus S., Bischoff P., Becker K. F., Höfler H. No evidence for mutations in the alpha- and beta-catenin genes in human gastric and breast carcinomas. Cancer Res. 1996 Jan 1;56(1):49–52. [PubMed] [Google Scholar]
  5. Fukuchi T., Sakamoto M., Tsuda H., Maruyama K., Nozawa S., Hirohashi S. Beta-catenin mutation in carcinoma of the uterine endometrium. Cancer Res. 1998 Aug 15;58(16):3526–3528. [PubMed] [Google Scholar]
  6. Ilyas M., Tomlinson I. P., Rowan A., Pignatelli M., Bodmer W. F. Beta-catenin mutations in cell lines established from human colorectal cancers. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10330–10334. doi: 10.1073/pnas.94.19.10330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Karnovsky A., Klymkowsky M. W. Anterior axis duplication in Xenopus induced by the over-expression of the cadherin-binding protein plakoglobin. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4522–4526. doi: 10.1073/pnas.92.10.4522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kawanishi J., Kato J., Sasaki K., Fujii S., Watanabe N., Niitsu Y. Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the beta-catenin gene in a human cancer cell line, HSC-39. Mol Cell Biol. 1995 Mar;15(3):1175–1181. doi: 10.1128/mcb.15.3.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kinzler K. W., Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996 Oct 18;87(2):159–170. doi: 10.1016/s0092-8674(00)81333-1. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Kolligs F. T., Kolligs B., Hajra K. M., Hu G., Tani M., Cho K. R., Fearon E. R. gamma-catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of beta-catenin. Genes Dev. 2000 Jun 1;14(11):1319–1331. [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Palacios J., Gamallo C. Mutations in the beta-catenin gene (CTNNB1) in endometrioid ovarian carcinomas. Cancer Res. 1998 Apr 1;58(7):1344–1347. [PubMed] [Google Scholar]
  15. Peifer M. Beta-catenin as oncogene: the smoking gun. Science. 1997 Mar 21;275(5307):1752–1753. doi: 10.1126/science.275.5307.1752. [DOI] [PubMed] [Google Scholar]
  16. Peifer M. Regulating cell proliferation: as easy as APC. Science. 1996 May 17;272(5264):974–975. doi: 10.1126/science.272.5264.974. [DOI] [PubMed] [Google Scholar]
  17. Rubinfeld B., Robbins P., El-Gamil M., Albert I., Porfiri E., Polakis P. Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science. 1997 Mar 21;275(5307):1790–1792. doi: 10.1126/science.275.5307.1790. [DOI] [PubMed] [Google Scholar]
  18. Rubinfeld B., Souza B., Albert I., Munemitsu S., Polakis P. The APC protein and E-cadherin form similar but independent complexes with alpha-catenin, beta-catenin, and plakoglobin. J Biol Chem. 1995 Mar 10;270(10):5549–5555. doi: 10.1074/jbc.270.10.5549. [DOI] [PubMed] [Google Scholar]
  19. Sacco P. A., McGranahan T. M., Wheelock M. J., Johnson K. R. Identification of plakoglobin domains required for association with N-cadherin and alpha-catenin. J Biol Chem. 1995 Aug 25;270(34):20201–20206. doi: 10.1074/jbc.270.34.20201. [DOI] [PubMed] [Google Scholar]
  20. Sparks A. B., Morin P. J., Vogelstein B., Kinzler K. W. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res. 1998 Mar 15;58(6):1130–1134. [PubMed] [Google Scholar]

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