β-catenin mutation in carcinoma of the uterine endometrium

Takeshi Fukuchi, Michiie Sakamoto, Hitoshi Tsuda, Keiji Maruyama, Shiro Nozawa, Setsuo Hirohashi

Research output: Contribution to journalArticle

337 Citations (Scopus)

Abstract

β-Catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator downstream of the Wnt signaling pathway. Activation of the pathway by stabilization of β-catenin has been shown to be important in the development of colorectal carcinoma, which is mainly caused by inactivating mutations of the adenomatous polyposis coli tumor suppressor gene or by activating mutations in exon 3 of the β-catenin gene. Here, we analyzed mutations in exon 3 of the β-catenin gene in endometrial carcinoma cases in which loss of heterozygosity at the adenomatous polyposis coil tumor suppressor gene locus has been rarely reported. We found that 10 of 76 cases had β-catenin gene mutations. All mutations identified were single-base missense mutations on serine/threonine residues (codons 33, 37, 41, and 45), altering the glycogen synthase kinase-3β phosphorylation consensus motif, which participates in the degradation of β-catenin. To determine whether these β-catenin mutations actually led to stabilization of this protein, expression of β-catenin was analyzed immunohistochemically, and 9 of 10 cases with the β-catenin mutation and 20 of 66 cases without it showed accumulation of β-catenin in the cytoplasm and/or nucleus. In total, 38% of cases showed accumulation of β-catenin. These data indicate that stabilization of β-catenin due to mutations in exon 3 of the β-catenin gene and other mechanisms may have an important role in development of endometrial carcinomas.

Original languageEnglish
Pages (from-to)3526-3528
Number of pages3
JournalCancer Research
Volume58
Issue number16
Publication statusPublished - 1998 Aug 15
Externally publishedYes

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Catenins
Endometrial Neoplasms
Mutation
Exons
Tumor Suppressor Genes
Genes
Glycogen Synthase Kinase 3
Wnt Signaling Pathway
Adenomatous Polyposis Coli
Loss of Heterozygosity
Missense Mutation
Threonine
Codon
Serine
Colorectal Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fukuchi, T., Sakamoto, M., Tsuda, H., Maruyama, K., Nozawa, S., & Hirohashi, S. (1998). β-catenin mutation in carcinoma of the uterine endometrium. Cancer Research, 58(16), 3526-3528.

β-catenin mutation in carcinoma of the uterine endometrium. / Fukuchi, Takeshi; Sakamoto, Michiie; Tsuda, Hitoshi; Maruyama, Keiji; Nozawa, Shiro; Hirohashi, Setsuo.

In: Cancer Research, Vol. 58, No. 16, 15.08.1998, p. 3526-3528.

Research output: Contribution to journalArticle

Fukuchi, T, Sakamoto, M, Tsuda, H, Maruyama, K, Nozawa, S & Hirohashi, S 1998, 'β-catenin mutation in carcinoma of the uterine endometrium', Cancer Research, vol. 58, no. 16, pp. 3526-3528.
Fukuchi T, Sakamoto M, Tsuda H, Maruyama K, Nozawa S, Hirohashi S. β-catenin mutation in carcinoma of the uterine endometrium. Cancer Research. 1998 Aug 15;58(16):3526-3528.
Fukuchi, Takeshi ; Sakamoto, Michiie ; Tsuda, Hitoshi ; Maruyama, Keiji ; Nozawa, Shiro ; Hirohashi, Setsuo. / β-catenin mutation in carcinoma of the uterine endometrium. In: Cancer Research. 1998 ; Vol. 58, No. 16. pp. 3526-3528.
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