Functional loss of E-cadherin and cadherin-11 alleles on chromosome 16q22 in colonic cancer.
Proteins of the cadherin family regulate cellular adhesion and motility and are believed to act as tumour suppressors. Previous studies have identified frequent mutation and allelic inactivation of the E-cadherin (cadherin-1) locus in diffuse gastric cancer. At least two other cadherin genes, P-cadherin (cadherin-3) and OB-cadherin (cadherin-11), have been mapped close to the E-cadherin gene on chromosome 16q22. As this region of the genome is frequently deleted in malignancy, multiple cadherin loci may be affected by losses of chromosome 16q22. The expression of mRNA transcripts from polymorphic alleles of the E-cadherin and cadherin-11 genes was examined in 30 cases of colonic, gastric, and renal carcinoma. In gastric cancer, loss of expression of one allele was restricted to the E-cadherin locus, whilst in renal carcinoma neither locus was affected. In colonic cancers, loss of expression of one E-cadherin allele was detected in 5 of 22 cases, whilst loss of a cadherin-11 allele was seen in 5 of 23 cases. This functional loss of cadherin gene expression may be due to gene deletion, inactivation or recombination. As no evidence of cadherin gene mutation was observed in the remaining transcripts, we can conclude that these two genes are only indirectly involved in the pathogenesis of colorectal cancer.
Braungart
E
E
Institut für Pathologie, GSF-Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany.
Schumacher
C
C
Hartmann
E
E
Nekarda
H
H
Becker
K F
KF
Höfler
H
H
Atkinson
M J
MJ
D015152:Blotting, Northern; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002885:Chromosomes, Human, Pair 16; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism; D019656:Loss of Heterozygosity; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015820:Cadherins; D009363:Neoplasm Proteins; C086960:osteoblast cadherin