The present inventors have shown that the
gene and
protein expression profiles of ADAM8, ADAM10 and ADAM12 in different grades and stages of
bladder cancer.ADAM12
gene expression was evaluated in tumors from 96 patients with
bladder cancer using a customized Affymetrix GeneChip.
Gene expression in
bladder cancer was validated using reverse transcription-
polymerase chain reaction (RT-PCR), quantitative PCR, and
in situ hybridization.
Protein expression was evaluated by immunohistochemical
staining on
tissue arrays of bladder cancers.The presence and relative amount of ADAM12 in the
urine of
cancer patients were determined by Western blotting and densitometric measurements, respectively.Particularly ADAM12
mRNA expression was significantly upregulated in bladder
cancer, as determined by
microarray analysis, and the level of ADAM12 mRNA correlated with
disease stage. ADAM12
protein expression correlated with tumor stage and grade. ADAM12 was present in higher levels in the
urine from bladder
cancer patients than in
urine from
healthy individuals. Significantly, following removal of tumor by
surgery, in most bladder cancer cases examined the level of ADAM12 in the urine decreased and, upon recurrence of tumor, increased.