Increased expression of estrogen‐related receptor α (ERRα) is a negative prognostic predictor in human prostate cancer

Abstract

The nuclear receptor ERRα (estrogen‐related receptor α) is known to modulate the estrogen‐signaling pathway, but the biological significance of ERRα in the prostate remains unclear. We investigated the expression of ERRα in human prostate tissues and cancer cell lines to evaluate the potential roles of the receptor in prostate cancer (PC). Western blot analysis of ERRα was performed in three cell lines of human PC (LNCaP, DU145 and PC‐3). The expressions of ERRα in cancerous lesions (n = 106) and benign foci (n = 99) of 106 surgically obtained prostate specimens were evaluated by immunohistochemistry. The relationships between the ERRα expression and clinicopathological features were evaluated. Western blot analysis using the polyclonal anti‐ERRα antibody detected a 52 kD band in all three PC cell lines. Positive immunostaining of ERRα in the nuclei was found in 73 (69%) cancerous and 47 (47.5%) benign epithelium, whereas the stromal tissues were negative for ERRα. The mean immunoreactivity score (IR score) of the cancerous lesions (3.5 ± 2.6) was significantly higher than that of the benign foci (1.8 ± 2.1) (p < 0.0001). The IR score of the cancerous lesions significantly correlated with the Gleason score (p = 0.0135). Univariate and multivariate hazard analyses revealed significant correlations between elevated ERRα expression and poor cancer‐specific survival (p = 0.0141 and 0.0367, respectively). The enhanced expression of ERRα might play a role in the development of human PC and serve as a significant prognostic factor for the disease. © 2006 Wiley‐Liss, Inc.

MicroRNA-125a Reduces Proliferation and Invasion of Oral Squamous Cell Carcinoma Cells by Targeting Estrogen-related Receptor α

“…Furthermore, ESRRA is up-regulated in several cancers, such as tumors of the breast, colorectum, prostate, and ovary (4 -8), reinforcing its potential role in tumorigenesis. More importantly, an increased level of ESRRA is linked to poor prognosis of breast, ovarian, and prostate tumors (7,9,10). Several reports suggest that the pharmacological modulation of ESRRA activity with specific inverse agonists such as XCT790 reduces proliferation of cell lines derived from breast, glial, lung, and cervical tumors (11)(12)(13)(14).…”

High expression of estrogen-related receptor α is significantly associated with poor prognosis in patients with colorectal cancer

“…Elevated ERRα expression in cancerous lesions was significantly correlated with poor cancer-specific survival rates in patients with prostate cancer (21). In human breast carcinoma, ERRα immunoreactivity was significantly associated with increased recurrence and shorter survival times (22).…”

“…Overall survival Disease-free survival of immunohistochemistry on prostate cancer specimens, researchers demonstrated that nuclear ERRα expression was significantly higher in the cancerous lesions compared with that in benign epithelia (21). Elevated ERRα expression in cancerous lesions was significantly correlated with poor cancer-specific survival rates in patients with prostate cancer (21).…”

WOMEN IN CANCER THEMATIC REVIEW: New roles for nuclear receptors in prostate cancer

“…Of the three subtypes, ERRα and ERRγ are the most consistently and prominently expressed in prostate cancer cells, tissue and xenografts at both RNA and protein levels; although ERRβ expression is high in normal prostate tissue, but lost in cancer (Cheung et al 2005). Expression of ERRα is inversely associated with prostate cancer outcome: in a cohort of 106 patients, ERRα expression increased in cancer compared with that in BPH and was significantly associated with poor prostate cancer-specific survival (Fujimura et al 2007). Consequently, ERRα has been reported to be pro-proliferative (Bianco et al 2009) whilst also providing protection against hypoxia (Zou et al 2014), and increasing prostate cancer cell invasiveness (Tribollet et al 2016).…”