Bladder Epithelial Cells: The Role of SETD6 on Bladder Cancer Growth and Survival
The Excretory System: Waste Removal Experts
Waste is removed from the body through an elegant filtration system that begins in the kidneys. The renal artery delivers blood to the kidneys, and in a series of filtration steps through the renal nephrons, waste products are removed from the blood to make up urine. Urine is then transferred to ducts called ureters, which deliver urine from the kidneys to the bladder. The bladder is a hollow muscular organ that collects the urine until it is expelled through the urethra.
Lifeline® offers bladder cells from different areas of the bladder, which can be used to study the normal function of the bladder, as well as bladder cancer. These include:
- Human Bladder Apex Epithelial Cells
- Human Bladder Dome Epithelial Cells
- Human Bladder Smooth Muscle Cells
- Human Bladder Fibroblasts
In addition, Lifeline®’s catalog includes cells from different parts of the kidney, including:
- Human Renal Medullary Epithelial Cells
- Human Renal Proximal Tubule Epithelial Cells
- Human Renal Cortical Epithelial Cells
- Human Renal Mixed Epithelial Cells
Lifeline® Human Bladder Epithelial Cells in Bladder Cancer Research
In the shadow of well-known cancers like lung and colorectal cancer, bladder cancer might get left behind. However, although less common in women, bladder cancer is the fourth most common cancer type in men, with 62,380 new cases predicted for 2018. While resection of non-invasive tumors has had some success, there is a high rate of tumor recurrence. In particular, activation of the NF-κB signaling pathway has been implicated in bladder cancer pathogenesis. Since NF-κB is ubiquitous and is important for the function of normal cells, targeting this pathway has been a challenge for therapeutic development. NF-κB is a transcription factor complex that is held in an inactive state by its negative regulator, IκB. In the presence of pro-inflammatory factors, IκB proteins are phosphorylated and subsequently degraded, releasing NF-κB to translocate to the nucleus, where it activates its transcriptional program.
NF-κB is regulated at multiple levels, and at the post-translational level, its activation is modulated in part by methylation of a member of the complex, p65, by SETD6. Although SETD6 is upregulated in some cancers, it is also downregulated in others. Given the unclear role of SETD6 in cancer, in a 2017 study in Oncotarget, Mukherjee and colleagues set out to define its role in bladder cancer. They first established the SETD6 expression profile using Lifeline® human bladder epithelial cells (HBLECs) and found that SETD6 transcript levels were low. In contrast, SETD6 transcript and protein expression was increased in bladder cancer cell lines and human bladder cancer samples.
To determine how increased SETD6 expression affects bladder cancer growth and survival, the authors performed knockdown and overexpression studies, which demonstrated that SETD6 expression confers increased growth and survival. The authors next examined the effects of SETD6 expression on activation of the NF-κB pathway and found that markers of activated NF-κB (increased p65 levels, increased p65 phosphorylation, and decreased IκB levels) were correlated with SETD6 levels, suggesting that SETD6 regulates activation of NF-κB.
To confirm this result, the authors demonstrated that overexpression of SETD6 increased p65 reporter activity and transcription of NF-κB target genes, including NQO1, CCL2, and MDM2. Together, the results of this study suggest that SETD6 is a positive regulator of NF-κB signaling and may represent a novel therapeutic target for the treatment of bladder cancer. In fact, the authors note that they have already identified a preliminary compound, palmatine, as a potential SETD6 inhibitor, which they are currently testing.
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Bladder cancer statistics from www.cancer.org.