The transmembrane protease serine 2:v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion is common in prostate cancer, while its functional role is not fully understood. The present study aimed to investigate the significance of the TMPRSS2:ERG gene fusion in human prostate cancers using bioinformatics tools. Comprehensive alteration analysis of TMPRSS2 and ERG in 148 different human cancer studies was performed by cBioPortal, and the mRNA expression level of the ERG gene was evaluated using Oncomine analysis. Furthermore, lentiviral short hairpin (sh)RNA-mediated knockdown of TMPRSS2:ERG was performed to study the impact of ERG silencing on cell proliferation and cell cycle distribution in prostate cancer cells. The results demonstrated that the TMPRSS2 and ERG genes were mostly altered in prostate cancer, and the most frequent alteration was gene fusion. Oncomine analysis demonstrated that the ERG gene was significantly upregulated in prostate clinical samples compared with the normal prostate gland in four independent datasets, and a positive association was observed between potassium inwardly-rectifying channel subfamily J member 15, down syndrome critical region gene 4, potassium inwardly-rectifying channel subfamily J member 6 and ERG gene expression. There were 272 mutations of the ERG gene identified in the cBioPortal database; among the mutations, 2 missense mutations (R367C and P401H) were regarded as functional mutations (functional impact score >1.938). Furthermore, the present study successfully knocked down ERG gene expression through a lentiviral-mediated gene silencing approach in VCaP prostate cancer cells. The ERG mRNA and protein expression levels were both suppressed significantly, and a cell-cycle arrest at G0/G1 phase was observed after ERG gene silencing. In conclusion, these bioinformatics analyses provide novel insights for TMPRSS2:ERG fusion gene study in prostate cancer. Target inhibition of ERG expression could significantly cause cell growth arrest in prostate cancer cells, which could be a potentially valuable target for prostate cancer treatment. However, the precise mechanism of these results remains unclear; therefore, further studies are required.
Prostate cancer (PCa) now remains the 2nd most frequently diagnosed cancer. In recent years, chemoprevention for PCa becomes a possible concept. Especially, many phytochemicals rich foods are suggested to lower the risk of cancer. Among these foods, green tea is considered as effective prevention for various cancers. However, clinical trials and previous meta-analyses on the relationship between green tea consumption and the risk of PCa have produced inconsistent outcomes. This study aims to determine the dose–response association of green tea intake with PCa risk and the preventive effect of green tea catechins on PCa risk. Seven observational studies and 3 randomized controlled trials were retrieved from Cochrane Library, PubMed, Sciencedirect Online, and hand searching. The STATA (version 12.0) was applied to analyze the data. The relative risks (RRs) and 95% confidence intervals were pooled by fixed or random effect modeling. Dose–response relations were evaluated with categories of green tea intake. Although there was no statistical significance in the comparison of the highest versus lowest category, there was a trend of reduced incidence of PCa with each 1 cup/day increase of green tea (P = 0.08). Our dose–response meta-analysis further demonstrated that higher green tea consumption was linearly associated with a reduced risk of PCa with more than 7 cups/day. In addition, green tea catechins were effective for preventing PCa with an RR of 0.38 (P = 0.02). In conclusion, our dose–response meta-analysis evaluated the association of green tea intake with PCa risk systematically and quantitatively. And this is the first meta-analysis of green tea catechins consumption and PCa incidence. Our novel data demonstrated that higher green tea consumption was linearly reduced PCa risk with more than 7 cups/day and green tea catechins were effective for preventing PCa. However, further studies are required to substantiate these conclusions.
Androgen and its receptor (AR) play an important role in maintaining spermatogenesis and male fertility. The nonclassical androgen signaling pathway is proposed to be mediated by an AR in plasma membrane in Sertoli cells. Our previous studies showed that testosterone induces cytoplasmic AR translocation to plasma membrane by binding with caveolin-1. This study was conducted to the underlying molecular mechanism mediating AR trafficking. Data from mass spectrometry using membrane coimmunoprecipitation sample by anti-AR antibody indicated VAPA is a candidate protein. Knockdown of VAPA by shRNA decreased the amount of AR localized to membrane and nuclear fraction and prevented AR trafficking after being exposed to testosterone. Further studies indicated AR trafficking in Sertoli cells might be mediated by VAPA via association with vesicle transport protein OSBP. This study can enrich the mechanism of the androgen actions and will be helpful for further clarifying the nonclassical signaling pathway of androgens in Sertoli cells.
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