Molecular analysis of E-cadherin and cadherin-11 in Wilms' tumours.
Different studies of Wilms' tumours have demonstrated a loss of heterozygosity (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 cell 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 be expressed in mesenchymal structures and developing epithelium, including renal tubules. For the present study, fresh frozen tissue from 30 Wilms' tumours and corresponding non-tumour tissues were analysed. Single nucleotide polymorphisms of the E-cadherin and cadherin-11 genes were chosen and analysed for allelic inactivation by polymerase chain reaction (PCR) amplification 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 cases (18%) showed loss of expression of one cadherin-11 allele. No length alterations of either the E-cadherin or the cadherin-11 messenger RNAs were identified using reverse transcription PCR and agarose gel electrophoresis in tumour tissue. Sequencing of the entire E-cadherin coding region in seven cases showed the wild-type sequence. These data imply that E-cadherin and cadherin-11 are not likely to play typical tumour suppressor roles in Wilms' tumour. Interestingly, the E-cadherin immunohistochemistry showed a deviation from the normal reaction pattern in 50% of the cases, with 27% (8/30) showing an apical or cytoplasmic reaction and 23% (7/30) being completely negative. Northern blot analysis revealed that the overall expression of cadherin-11 is much stronger than that of E-cadherin. In several cases, the expression levels of the two genes were inversely correlated, suggesting the existence of a regulatory mechanism. Analysis of differential expression of the various cadherins and their subsequent signal transduction pathways might contribute to a better understanding of the complexity of Wilms' tumour formation.
Schulz
S
S
Institut für Allgemeine Pathologie und Pathologische Anatomie der Technischen Universität München, Klinikum rechts der Isar, Munich, Germany.
Becker
K F
KF
Braungart
E
E
Reichmuth
C
C
Klamt
B
B
Becker
I
I
Atkinson
M
M
Gessler
M
M
Höfler
H
H
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005260:Female; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007680:Kidney Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D009396:Wilms Tumor / Q000235:genetics*
D015820:Cadherins; C086960:osteoblast cadherin