BERKELEY, CA (UroToday.com) - Sex steroid hormones have been implicated in bladder carcinogenesis by binding to specific estrogen receptor (ER) subtypes: ERα and ERβ, which is the predominant type.
However, the expression of ERβ and its co-regulators, p300 (co-activator) and NCoR (nuclear receptor co-repressor), have not been extensively studied in bladder cancer. Recently, Kontos et al.  studied the expression of these molecules and correlated them with clinical-pathological parameters. One hundred and eleven consecutive patients, aged 23 to 90 years, with transitional-cell cancer of the bladder were included in this prospective study. The authors demonstrated that ERβ was more frequently expressed in the nucleus of normal bladder epithelium compared to malignant bladder epithelium with statistical significant association (p = 0.003). The p300 was expressed only in the nucleus of bladder cancer cells and a statistically significant, positive correlation between molecular expression and cancer progression was demonstrated (p<0.001).
NCoR immunostaining was demonstrated in the nuclei of bladder cells, which was significantly higher in normal tissue than in cancer cells (p<0.001), with a negative correlation. Also, its expression in grade I tumors was significantly higher than in grade II (p<0.001) and grade III tumors (p<0.001). Therefore, this study showed that ERβ expression was significantly lower in poorly differentiated bladder cancer cells, and this progressive decline correlated with the loss of cancer cell proliferation, suggesting a protective role of ERβ during bladder carcinogenesis. For the nuclear expression of the co-activator p300, a positive correlation was demonstrated with bladder cancer progression. Regarding the co-repressor NCoR, its nuclear expression negatively correlated with bladder carcinogenesis. Between p300 and NCoR, there might be a reciprocal transactivation in a cell-type-dependent manner. These 2 co-regulators may not be strictly segregated and may interact directly, as p300 may interact negatively with NCoR. During bladder carcinogenesis, the reduced expression of NCoR and the loss of its inhibitory role on p300 transcriptional activity may play a role in tumorigenicity. Overexpression of p300 reduces the inhibitory role of ERβ on nuclear factor-κB-dependent transcription, which contributes to malignant transformation. The challenge for the future will be to determine and develop molecules that will manipulate ERβ and its co-regulators, p300 and NCoR.
- Kontos S, Papatsoris A, Kominea A, Melachrinou M, Tanoglidi A, Kachrilas S, et al. Expression of ERβ and Its Co-Regulators p300 and NCoR in Human Transitional Cell Bladder Cancer. Urol Int. 2011;87(2):151-158.
Athanasios Papatsoris MD, MSc, PhD, FEBU, FES., as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.