Over-expression and amplification of the c-myc gene in human urothelial carcinoma.
To understand the mechanisms underlying increased expression of Myc protein in human urinary bladder cancer, expression of c-myc mRNA and the copy number of the c-myc gene were determined. Expression of mRNA was measured by quantitative RT-PCR in 40 urothelial carcinomas and in 18 histologically normal mucosae. Mean expression in tumors was significantly increased (3.23+/-2.63 AU vs. 1.90+/-0.95 AU, p < 0.023) and exceeded the highest level in normal mucosa in 15 (37.5%) tumors. The c-myc gene copy number was higher than in leukocytes and normal bladder mucosa in 14 of 40 tumors, but only 3 among these showed a more than 4-fold increase indicative of gene amplification. Most, but not all, tumors with elevated expression displayed an increased gene copy number (p < 0.0001). In line with other studies of the protein level, no significant association either of c-myc mRNA over-expression or of increased gene copy number with tumor stage or grade was observed. The data indicate that elevated mRNA expression as a consequence of increases in c-myc gene copy number often underlies Myc protein over-expression in bladder cancer. This increase may be a consequence of, most frequently, chromosome 8q gain and, occasionally, gene amplification, while in some tumors deregulation of mRNA expression occurs without evident changes in the c-myc gene copy number.
Christoph
F
F
Urologische Klinik, Heinrich-Heine-Universität, Düsseldorf, Germany.
Schmidt
B
B
Schmitz-Dräger
B J
BJ
Schulz
W A
WA
D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger