Molecular analysis of E-cadherin and cadherin-II in Wilms' tumours

Citation
S. Schulz et al., Molecular analysis of E-cadherin and cadherin-II in Wilms' tumours, J PATHOLOGY, 191(2), 2000, pp. 162-169
Citations number
38
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF PATHOLOGY
ISSN journal
00223417 → ACNP
Volume
191
Issue
2
Year of publication
2000
Pages
162 - 169
Database
ISI
SICI code
0022-3417(200006)191:2<162:MAOEAC>2.0.ZU;2-G
Abstract
Different studies of Wilms' tumours have demonstrated a loss of heterozygos ity (LOH) of chromosome 16q ranging from 17 to 25%. In order to search for a potential tumour suppressor gene on 16q, we chose the calcium-dependent c ell adhesion molecules E-cadherin and cadherin-11 as candidate genes, which are both located on the long arm of chromosome 16, E-cadherin is known to be expressed in epithelial structures, whereas cadherin-11 is supposed to b e expressed in mesenchymal structures and developing epithelium, including renal tubules. For the present study, fresh frozen tissue from 30 Wilms' tu mours and corresponding non-tumour tissues were analysed. Single nucleotide polymorphisms of the E-cadherin and cadherin-11 genes were chosen and anal ysed for allelic inactivation by polymerase chain reaction (PCR) amplificat ion and sequence analysis. Loss of expression of one E-cadherin allele was seen in 10% (2/20) of the informative cases. Two out of 11 informative case s (18%) showed loss of expression of one cadherin-11 allele. No length alte rations of either the E-cadherin or the cadherin-11 messenger RNAs were ide ntified using reverse transcription PCR and agarose gel electrophoresis in tumour tissue. Sequencing of the entire E-cadherin coding region in seven c ases showed the wild-type sequence. These data imply that E-cadherin and ca dherin-11 are not likely to play typical tumour suppressor roles in Wilms' tumour. Interestingly, the E-cadherin immunohistochemistry showed a deviati on from the normal reaction pattern in 50% of the cases, with 27% (8/30) sh owing an apical or cytoplasmic reaction and 23% (7/30) being completely neg ative. Northern blot analysis revealed that the overall expression of cadhe rin-11 is much stronger than that of E-cadherin. In several cases, the expr ession levels of the two genes were inversely correlated, suggesting the ex istence of a regulatory mechanism. Analysis of differential expression of t he various cadherins and their subsequent signal transduction pathways migh t contribute to a better understanding of the complexity of Wilms' tumour f ormation. Copyright (C) 2000 John Wiley Br Sons, Ltd.