Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder.

TitleIncreased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder.
Publication TypeJournal Article
Year of Publication2005
AuthorsRaman JD, Mongan NP, Tickoo SK, Boorjian SA, Scherr DS, Gudas LJ
JournalClin Cancer Res
Issue24 Pt 1
Date Published2005 Dec 15
KeywordsAdult, Aged, Aged, 80 and over, Carcinoma, Transitional Cell, Cell Line, Tumor, DNA-Binding Proteins, Enhancer of Zeste Homolog 2 Protein, Female, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, Polycomb Repressive Complex 2, RNA, Messenger, RNA, Neoplasm, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Urinary Bladder, Urinary Bladder Neoplasms

PURPOSE: The Polycomb group gene, EZH2, functions as a transcriptional repressor involved in gene silencing. Amplification of EZH2 has been reported in several malignancies, including prostate, breast, and lymphoma. We evaluated EZH2 mRNA and protein expression in bladder specimens from patients and the EZH2 mRNA expression in five bladder cancer cell lines.

EXPERIMENTAL DESIGN: EZH2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR) in 38 bladder tissue specimens. We also evaluated 39 bladder cancer specimens for EZH2 protein expression using immunohistochemistry with affinity-purified antibodies to human EZH2. In addition, five human bladder cancer cell lines were analyzed by RT-PCR for EZH2 mRNA expression.

RESULTS: Five of 14 (36%) nontumor bladder specimens versus 21 of 24 (88%) bladder tumors showed EZH2 mRNA expression (P=0.003). All of the invasive tumors (10 of 10) had detectable EZH2 mRNA expression, compared with 11 of 14 (79%) superficial tumors. In addition, EZH2 mRNA expression was noted in 100% (16 of 16) of high-grade bladder tumors versus 50% (4 of 8) of low-grade tumors (P=0.01). EZH2 protein expression, meanwhile, was increased in neoplastic tissue compared with nontumor urothelium (78% versus 69% of nuclei, P<0.005). There were no differences in EZH2 protein levels between superficial and invasive tumors. High-grade tumors had increased EZH2 staining compared with normal urothelium (78% versus 68%, P<0.005), whereas low-grade lesions did not. Four of five human bladder cancer cell lines expressed high levels of EZH2, whereas only low levels were detected in one cell line.

CONCLUSIONS: We report a significant increase in EZH2 expression in transitional cell carcinoma of the bladder compared with normal urothelium. These data suggest that similar to other human malignancies, increased EZH2 expression correlates with oncogenesis of the bladder.

Alternate JournalClin. Cancer Res.
PubMed ID16361539
Grant ListR01CA097543 / CA / NCI NIH HHS / United States
R01DE10389 / DE / NIDCR NIH HHS / United States