Pp. Bringuier et al., EXPRESSION OF CYCLIN D1 AND EMS1 IN BLADDER-TUMORS - RELATIONSHIP WITH CHROMOSOME 11Q13 AMPLIFICATION, Oncogene, 12(8), 1996, pp. 1747-1753
11q13 amplifications have been found in several cancers, including bla
dder tumours,However, the biological significance of this genetic alte
ration is not yet fully understood, To get more insight into the role
of 11q13 amplification in bladder tumour development, we have studied
the level of amplification and expression of 4 (protoonco)genes lying
within the amplicon: cyclin D1, FGF3, FGF4 and EMS1 DNA amplification
was found in 5/46 tumours, There was no correlation between amplificat
ion and clinico-pathological data. No expression of FGF3 and FGF4 was
detected whereas both cyclin D1 and EMS1 were expressed at higher leve
l in tumours with amplifications, Thus cyclin D1 and EMS1, but not FGF
3 and FGF4, are likely to play a pathogenic role in the 11q13 amplific
ation in bladder cancer, However, amplification is not the unique way
of activation of these genes, Indeed, in situ hybridisation and Northe
rn blot analysis have shown that most bladder tumours have a fair to h
igh expression of cyclin D1 and EMS1 in contrast to normal urothelium
with a moderate expression, Interestingly, a trend towards higher expr
ession occurs in superficial versus invasive tumours (8.8+/-2.0 versus
1.9+/-0.4; P approximate to 13% for cyclin D1 and 4.5 +/- 1.4 versus
2.0 +/- 0.4; P approximate to 8% for EMS1), Moreover, the 9 tumours wi
th low expression are all highly malignant, leading to the hypothesis
that the tumours developing through a cyclin D1/EMS1 independent pathw
ay are more aggressive.