PMID- 21525722 OWN - NLM STAT- MEDLINE DCOM- 20120117 LR - 20110913 IS - 1423-0399 (Electronic) IS - 0042-1138 (Linking) VI - 87 IP - 2 DP - 2011 TI - Expression of ERbeta and its co-regulators p300 and NCoR in human transitional cell bladder cancer. PG - 151-8 LID - 10.1159/000324262 [doi] AB - OBJECTIVE: Several data support a possible role of estrogens in bladder carcinogenesis, mediated mainly through estrogen receptor-beta (ERbeta). We study the expression of ERbeta and its co-regulators p300 and nuclear co-repressor (NCoR) in patients with bladder cancer. PATIENTS AND METHODS: One hundred and eleven consecutive patients (74 males and 37 females), aged 23-90 years (mean 70 +/- 10) diagnosed with transitional cell bladder cancer were included in this study. The control group consisted of 29 patients that underwent transurethral prostatectomy and consented to simultaneous bladder biopsies. Immunohistochemical studies took place on formalin-fixed, paraffin-embedded sections from the TUR (transurethral resection) specimens. We studied the expression of ERbeta, p300 and NCoR.chi(2) test was used to evaluate the relationship between the histological grade and ERbeta expression, grade and co-regulators expression and grade and gender. Spearman rank correlation coefficient (r) was used in order to estimate the direction and strength of correlations between histological grade and ERbeta-p300-NCoR expressions. The Cochran-Armitage test for trend was applied in order to examine possible trends across the ordered levels of histological grade. RESULTS: ERbeta was more frequently expressed in the nucleus of normal bladder epithelium compared to malignant bladder epithelium with statistical significant association (r = -0.25, p = 0.003). The p300 was expressed only in the nucleus of bladder cancer cells and a positive correlation between molecular expression and cancer progression was demonstrated (r = 0.55, p < 0.001). NCoR immunostaining was demonstrated in the nuclei of bladder cells. Nuclear staining was significantly higher in normal tissue than in cancer cells (r = -0.33, p < 0.001), with negative correlation. Furthermore, its expression in grade I tumors was significantly higher than in grade II (r = -0.46, p < 0.001) and grade III tumors (r = -0.51, p < 0.001). Thus, like ERbeta, NCoR expression in bladder epithelium decreased during cancer progression and loss of cell differentiation. There was no correlation between the levels of expression of the three proteins in normal bladder epithelium, but there was an inverse correlation between the nuclear expression of ERbeta and p300 in carcinomas (r = -3.88, p = 0.042). Statistical significant association was established when correlating ERbeta expression with NCoR expression (r = 0.273, p = 0.005), while co-regulators' nuclear expression did not correlate with each other (p > 0.05). CONCLUSIONS: In bladder carcinogenesis, we demonstrated inhibition in the expression of ERbeta and its co-repressor NCoR as well as increased expression of the co-activator p300. CI - Copyright (c) 2011 S. Karger AG, Basel. FAU - Kontos, Stylianos AU - Kontos S AD - Department of Anatomy and Histology, School of Medicine, University of Patras, Patras, Greece. FAU - Papatsoris, Athanasios AU - Papatsoris A FAU - Kominea, Athina AU - Kominea A FAU - Melachrinou, Maria AU - Melachrinou M FAU - Tanoglidi, Anna AU - Tanoglidi A FAU - Kachrilas, Stefanos AU - Kachrilas S FAU - Karavitakis, Markos AU - Karavitakis M FAU - Balampani, Eleni AU - Balampani E FAU - Sotiropoulou-Bonikou, Georgia AU - Sotiropoulou-Bonikou G LA - eng PT - Journal Article DEP - 20110422 PL - Switzerland TA - Urol Int JT - Urologia internationalis JID - 0417373 RN - 0 (Estrogen Receptor beta) RN - 0 (NCOR1 protein, human) RN - 0 (Nuclear Receptor Co-Repressor 1) RN - EC 2.3.1.48 (E1A-Associated p300 Protein) RN - EC 2.3.1.48 (EP300 protein, human) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Transitional Cell/*metabolism MH - Disease Progression MH - E1A-Associated p300 Protein/*biosynthesis MH - Epithelium/pathology MH - Estrogen Receptor beta/*biosynthesis MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Male MH - Middle Aged MH - Nuclear Receptor Co-Repressor 1/*biosynthesis MH - Prognosis MH - Urinary Bladder Neoplasms/*metabolism EDAT- 2011/04/29 06:00 MHDA- 2012/01/18 06:00 CRDT- 2011/04/29 06:00 PHST- 2010/07/27 00:00 [received] PHST- 2011/01/04 00:00 [accepted] PHST- 2011/04/29 06:00 [entrez] PHST- 2011/04/29 06:00 [pubmed] PHST- 2012/01/18 06:00 [medline] AID - 000324262 [pii] AID - 10.1159/000324262 [doi] PST - ppublish SO - Urol Int. 2011;87(2):151-8. doi: 10.1159/000324262. Epub 2011 Apr 22.