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

Jay Raman, Nigel P. Mongan, Satish K. Tickoo, Stephen A. Boorjian, Douglas S. Scherr, Lorraine J. Gudas

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8570-8576
Number of pages7
JournalClinical Cancer Research
Volume11
Issue number24
DOIs
StatePublished - Dec 15 2005

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Transitional Cell Carcinoma
Urinary Bladder Neoplasms
Urinary Bladder
Messenger RNA
Urothelium
Genes
Neoplasms
Cell Line
Reverse Transcription
Proteins
Polymerase Chain Reaction
Antibody Affinity
Gene Silencing
Prostate
Lymphoma
Carcinogenesis
Breast
Research Design
Immunohistochemistry
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Raman, Jay ; Mongan, Nigel P. ; Tickoo, Satish K. ; Boorjian, Stephen A. ; Scherr, Douglas S. ; Gudas, Lorraine J. / Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 24. pp. 8570-8576.
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title = "Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder",
abstract = "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.",
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Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder. / Raman, Jay; Mongan, Nigel P.; Tickoo, Satish K.; Boorjian, Stephen A.; Scherr, Douglas S.; Gudas, Lorraine J.

In: Clinical Cancer Research, Vol. 11, No. 24, 15.12.2005, p. 8570-8576.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Increased expression of the polycomb group gene, EZH2, in transitional cell carcinoma of the bladder

AU - Raman, Jay

AU - Mongan, Nigel P.

AU - Tickoo, Satish K.

AU - Boorjian, Stephen A.

AU - Scherr, Douglas S.

AU - Gudas, Lorraine J.

PY - 2005/12/15

Y1 - 2005/12/15

N2 - 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.

AB - 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.

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