Although primary human PCa-associated fibroblasts and the human WPMY-1-reactive prostate stromal cell line maintain this inherent estrogen receptor (ER)β-dependent motility inhibitor activity, they are subverted by TGF-β1 pro-oxidant signals derived from cocultured DU145 PCa cells.
These findings suggest that CCND1 expression is possibly regulated by estrogens via ERβ and that this signaling pathway may influence prostate cancer development.
Differential expression profile analysis of ERβ was analyzed by quantitative immunohistochemistry using ethnicity-based tissue microarray encompassing 300 PCa tissue cores.
We have previously demonstrated the metastasis-promoting effect of an estrogen receptor beta (ERβ) agonist (genistein) in a patient-derived PCa xenograft model mimicking localized and metastatic disease.
In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa).
The result also showed that there was a significant association between ESR2rs1256049 polymorphism and prostate cancer in Caucasians (AA+AG vs. GG: P = 0.016; A vs. G: P = 0.005), but no association in overall populations (AA+AG vs. GG: P = 0.826; A vs. G: P = 0.478), Asians (AA+AG vs. GG: P = 0.177; A vs. G: P = 0.703) and Africans (AA+AG vs. GG: P = 0.847; A vs. G: P = 0.707).
These findings reveal a novel fulvestrant signaling cascade involving ERβ-mediated transcriptional upregulation of hsa-miR-765 that suppresses HMGA1 protein expression as part of the mechanism underlying the tumor suppressor action of fulvestrant in prostate cancer.
Although, an increasing body of evidence has linked estrogen receptor beta (ERß) to prostate cancer, the function of estrogen receptor alpha (ERα) in prostate cancer is not very well studied.
We identify two independent susceptibility loci for prostate cancer at 11p15.4 (rs12791447, P=3.59 × 10(-8); PPFIBP2) and 14q23.2 (rs58262369, P=6.05 × 10(-10); ESR2).
These findings provide a novel mechanism for how ERβ prevents NF-κB activation and raise the exciting possibility that loss of ERβ expression is linked to chronic inflammation in the prostate, which contributes to the development of high-grade prostate cancer.
ERβ is epigenetically silenced in prostate cancer patients, therefore our results suggest that combination of ERβ agonists with ADT would benefit men stratified on the basis of high estrogen levels.
Our results suggest that the estrogen receptor ESR2 has a very important function to predict PCa and that different SNPs have different predictive values.
Taken together, our results support the conclusion that abnormal methylation of the ERβ promoter may increase genetic susceptibility to prostate cancer.