Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p < 0.05) increased expression of GRβ compared to UMUC-3, which also correlated with higher migration rates. Knockdown of GRβ in the T24 cells resulted in a decreased migration rate. Mutational analysis of the 3′ untranslated region (UTR) of human GRβ revealed that miR144 might positively regulate expression. Indeed, overexpression of miR144 increased GRβ by 3.8 fold. In addition, miR144 and GRβ were upregulated during migration. We used a peptide nucleic acid conjugated to a cell penetrating-peptide (Sweet-P) to block the binding site for miR144 in the 3′UTR of GRβ. Sweet-P effectively prevented miR144 actions and decreased GRβ expression, as well as the migration of the T24 human bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

Bladder cancer is encountered worldwide having been associated with a host of environmental and lifestyle risk factors. The disease has a male to female prevalence of 3 : 1. This disparity has raised the possibility of the androgen receptor (AR) pathway being involved in the genesis of the disease; indeed, research has shown that AR is involved in and is likely a driver of bladder cancer. Similarly, an inflammatory response has been implicated as a major player in bladder carcinogenesis. Consistent with this concept, recent work on anti-inflammatory glucocorticoid signaling points to a pathway that may impact bladder cancer. The glucocorticoid receptor- (GR-) α isoform has an important role in suppressing inflammatory processes, which may be attenuated by AR in the development of bladder cancer. In addition, a GR isoform that is inhibitory to GRα, GRβ, is proinflammatory and has been shown to induce cancer growth. In this paper, we review the evidence of inflammatory mediators and the relationship of AR and GR isoforms as they relate to the propensity for bladder cancer.

prostate disease (BPD) between subjects with and without H. pylori infection. In animal study, subcutaneous dorsal H. pylori protein extract injection in time sequential manner was used to induce chronic reaction. Systemic and prostate inflammation were evaluated by checking splenic tumor necrosis factor alpha (TNF-a), interleukin-1 beta (IL-1b), and prostatic nuclear factor-kappa B (NF-kB) respectively. Prostate was stained to confirm the location of these responses.RESULTS: Of the 24878 sampled subjects, 3688 (14.8%) had developed BPD after the index date; BPD was found in 2008 (16.1%) cases and 1680 (13.5%) controls (p<0.001). Regression analysis revealed, the OR for BPD among cases was 1.215 (95% CI ¼ 1.130-1.306, p<0.001) after adjusting for diabetes, hypertension, hyperlipidemia, coronary artery disease, urinary tract infection, and urolithiasis. In rats with protein extract injection, increased tactile hypersensitivity in scrotal base was found 15 days after injection. There were Increased TNF-a and IL-1b. Prostate inflammation was also confirmed by NF-kb and Caspase 1 staining, which was compatible with physiological changes in rats.CONCLUSIONS: There may be some link between H.pylori protein exposure and prostate inflammation. Our analysis may be only a part of the whole picture. Local prostatic inflammation may be induced by distant antigen-related systemic response.