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Abnormalities of the APC/beta-catenin pathway in endometrial cancer.

Authors: Moreno-Bueno, Gema  Hardisson, David  Sánchez, Carolina  Sarrió, David  Cassia, Raúl  García-Rostán, Ginesa  Prat, Jaime  Guo, Mingzhou  Herman, James G  Matías-Guiu, Xavier  Esteller, Manel  Palacios, José 
Citation: Moreno-Bueno G, etal., Oncogene. 2002 Nov 14;21(52):7981-90.
Pubmed: (View Article at PubMed) PMID:12439748
DOI: Full-text: DOI:10.1038/sj.onc.1205924

The activation of the APC/beta-catenin signalling pathway due to beta-catenin mutations has been implicated in the development of a subset of endometrial carcinomas (ECs). However, up to 25% of ECs have beta-catenin nuclear accumulation without evidence of beta-catenin mutations, suggesting alterations of other molecules that can modulate the Wnt pathway, such as APC, gamma-catenin, AXIN1 and AXIN2. We investigated the expression pattern of beta- and gamma-catenin in a group of 128 endometrial carcinomas, including 95 endometrioid endometrial carcinomas (EECs) and 33 non-endometrioid endometrial carcinomas (NEECs). In addition, we evaluated the presence of loss of heterozygosity and promoter hypermethylation of the APC gene and mutations in the APC, beta- and gamma-catenin, AXIN1, AXIN2, and RAS genes, and phospho-Akt expression. No APC mutations were detected but LOH at the APC locus was found in 24.3% of informative cases. APC promoter 1A hypermethylation was observed in 46.6% of ECs, and was associated with the endometrioid phenotype (P=0.034) and microsatellite instability (P=0.008). Neither LOH nor promoter hypermethylation of APC was associated with nuclear catenin expression. Nuclear beta-catenin expression was found in 31.2% of EECs and 3% of NEECs (P=0.002), and was significantly associated with beta-catenin gene exon 3 mutations (P<0.0001). beta-catenin gene exon 3 mutations were associated with the endometrioid phenotype, and were detected in 14 (14.9%) EECs, but in none of the NEECs (P=0.02). gamma-catenin nuclear expression was found in 10 ECs; it was not associated with the histological type but was associated with more advanced stages (P=0.042). No mutations in gamma-catenin, AXIN1 and 2 genes were detected in this series. Neither RAS mutations nor phospho-Akt expression, which were found in 16 and 27.6% of the cases, respectively, were associated with beta-catenin nuclear expression. Our results demonstrated a high prevalence of alterations in molecules of the APC/beta-catenin pathway, but only mutations in beta-catenin gene are associated with aberrant nuclear localization of beta-catenin.

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CRRD Object Information
CRRD ID: 13432145
Created: 2017-09-21
Species: All species
Last Modified: 2017-09-21
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.