Bladder cancer originated from urothelium belongs to the top ten among all tumors. Various factors like genetic and molecular defects, appearance of different tumors in the family, previous genitourinary disorders and exposure to chemical compounds are reported as potential causes of this type of cancer. It has been reported that TP53, p21 or Ras mutations and epigenetic alterations of genes coding for these oncogenes are involved in the aetiology of urothelium originating bladder cancer. Additionally, the TCGA study indicated that such important regulatory pathways/machineries like these controlling cell cycle; (PI(3)K)/AKT/mTOR signaling involved in the metabolism control; and chromatin modificators including SWI/SNF chromatin remodeling complex (CRC) are affected in this disease.
Immunohistochemistry (IHC) on paraffin embedded clinical samples for SWI/SNF core subunits and key enzymes involved in metabolism control, comparative transcriptomic study and confirmatory quantitative real-time PCR (qRT-PCR) were used in this work.
In this study we found a substantial decrease of protein levels of SWI/SNF core subunits in bladder cancer clinical samples. Subsequently, we performed reanalysis of transcriptomic data for clinical samples obtained from GEO database and confirmatory assessment of the transcript level in clinical samples. This analysis showed that the reduced protein level of SWI/SNF core subunits observed in advanced bladder cancer is likely caused by the decreased abundance of corresponding transcripts. We also found that the SWI/SNF complex interacts in human cells with key proteins involved in the control of energy status and glucose metabolism. The IHC analysis indicated altered abundance of these enzymes in cancer cells when compared to normal urothelium consistently to strong metabolic alterations characteristic for this type of cancer.
The down-regulation of SWI/SNF complex on both transcript and protein level, and decreased activity of its partner proteins link the molecular features with metabolic alterations observed in this type of cancer.
Clinical trial identification
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This work was supported by grant from National Science Center No UMO–2014/13/B/NZ2/01187
All authors have declared no conflicts of interest.