EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer
| Autor: | Robert L. Sutherland, Amanda J. Russell, Davendra Segara, Neville F. Hacker, Graham J. Mann, David Y.H. Choong, Tania Nolan, Michelle J. Henderson, David W. Anderson, Ged Brady, Michael J. Davies, Susan M. Henshall, Erica Woollatt, Graeme A. Macdonald, Olufunmilayo I. Olopade, Ronaldo J. Bova, Jennifer L. Clancy, Colin K. W. Watts, Ian G. Campbell |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
Ubiquitin-Protein Ligases Breast Neoplasms Locus (genetics) Biology Loss of heterozygosity Breast cancer Neoplasms Gene duplication Genetics medicine Humans Copy-number variation Peptide Synthases Allele Molecular Biology Chromosome Aberrations Ovarian Neoplasms Cancer medicine.disease body regions Cancer research Female Ovarian cancer Chromosomes Human Pair 8 Microsatellite Repeats |
| Zdroj: | Oncogene. 22:5070-5081 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | EDD (E3 isolated by differential display), located at chromosome 8q22.3, is the human orthologue of the Drosophila melanogaster tumour suppressor gene 'hyperplastic discs' and encodes a HECT domain E3 ubiquitin protein-ligase. To investigate the possible involvement of EDD in human cancer, several cancers from diverse tissue sites were analysed for allelic gain or loss (allelic imbalance, AI) at the EDD locus using an EDD-specific microsatellite, CEDD, and other polymorphic microsatellites mapped in the vicinity of the 8q22.3 locus. Of 143 cancers studied, 38 had AI at CEDD (42% of 90 informative cases). In 14 of these cases, discrete regions of imbalance encompassing 8q22.3 were present, while the remainder had more extensive 8q aberrations. AI of CEDD was most frequent in ovarian cancer (22/47 informative cases, 47%), particularly in the serous subtype (16/22, 73%), but was rare in benign and borderline ovarian tumours. AI was also common in breast cancer (31%), hepatocellular carcinoma (46%), squamous cell carcinoma of the tongue (50%) and metastatic melanoma (18%). AI is likely to represent amplification of the EDD gene locus rather than loss of heterozygosity, as quantitative RT-PCR and immunohistochemistry showed that EDD mRNA and protein are frequently overexpressed in breast and ovarian cancers, while among breast cancer cell lines EDD overexpression and increased gene copy number were correlated. These results demonstrate that AI at the EDD locus is common in a diversity of carcinomas and that the EDD gene is frequently overexpressed in breast and ovarian cancer, implying a potential role in cancer progression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|