Allelic imbalance at the beta-catenin gene (CTNNB1 at 3p22-21.3) in various human tumor types

Nollet, Friedel; Vandenberg, Albert; Kersemaekers, Anne-Marie F.; Cleton-Jansen, Anne Marie; Berx, Geert; Vanderveen, Ay; Eichperger, C; Wieland, I.; DeGreve, J; Liefers, G.J.; Xiao, Wenqin; Buys, Charles H.C.M.; Cj, Cornelisse; Vanroy, F

doi:10.3892/ijo.11.2.311

Cited by 2 publications

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“…Mutations in the b-catenin gene are infrequent in ovarian carcinoma and interestingly only described in the endometrioid type of epithelial ovarian tumours (Palacios and Gamallo, 1998;Wright et al, 1999). Allelic imbalance has not been found in the b-catenin gene in ovarian cancers (Nollet et al, 1997), but histological grade was not stated in their study. The Tcf-Lef family, members of the HMG-box transcription factors, are expressed in the normal epithelium from different organs, localised to the nucleus or the cytoplasm (Barker et al, 1999).…”

Section: Discussionmentioning

confidence: 72%

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

et al. 2003

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Beta-catenin is involved in both cell -cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of b-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3b (GSK3b) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed b-catenin, APC, GSK3b and Lef-1. Nuclear staining of b-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of b-catenin and GSK3b, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of b-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of b-catenin could be due to an increased binding to the cadherin -a-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of b-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.

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Section: Discussionmentioning

confidence: 72%

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

et al. 2003

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“…Frequent co-deletion of flanking chromosomal regions was observed. However, a small cell lung cancer cell line, containing a small homozygously deleted region within this chromosomal locus, was found to retain the p-catenin gene (Kok et al, 1994;Nollet et al, 1997). LOH is one of the major mutational events affecting tumour suppressor genes.…”

Section: Mutations Affecting the P-catenin Functionmentioning

confidence: 99%

Dysregulation of the E-Cadherin/Catenin Complex by Irreversible Mutations in Human Carcinomas

Berx

Nollet

Roy

1998

Cell Adhesion and Communication

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The different proteins of the E-cadherinicatenin cell-cell adhesion complex are believed to play a predominant role in carcinogenesis. Aberrant expression of these proteins has been found in many different human carcinomas, indicating abnormal regulation. In general, inactivating mutations of the human E-cadherin gene are rare; they are, however, highly frequent in infiltrating lobular breast carcinomas and in diffuse gastric carcinomas. These mutations mostly occur in combination with loss of heterozygosity (LOH) of the wild-type allele. Mutations were found at very early non-invasive stages, thus associating E-cadherin mutations with loss of growth control and defining E-cadherin as a real tumour suppressor for these particular tumour types. Defects affecting both alleles of the crE-catenin gene have been found in different human carcinoma cell lines, resulting in the loss of E-cadherin-mediated cell-cell adhesion. Mutations of the /?-catenin gene in colon tumours and melanomas were found to result in an accumulation of the protein in the cytosol. Upon translocation to the nucleus, this p-catenin enhances TCF/LEF-dependent transcriptional activity. This suggests that mutated p-catenin can act as an oncogene in these particular tumour types. The multiple interaction partners of P-catenin are known to be involved in signal transduction, actin organization, protein phosphorylation or transcriptional regulation. This makes this protein an intriguing alternative target for either activation or inactivation in human cancer types characterized by frequent E-cadherin or APC deficiencies.

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Allelic imbalance at the beta-catenin gene (CTNNB1 at 3p22-21.3) in various human tumor types

Cited by 2 publications

References 0 publications

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

Dysregulation of the E-Cadherin/Catenin Complex by Irreversible Mutations in Human Carcinomas

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