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Differential expression of potassium ion channels in human renal cell carcinoma
Surbhi Wadhwa1, Pankaj Wadhwa, Amit K Dinda
1Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Purpose:
Ether-a-go-go (EAG) or EAG-related (ERG) voltage-gated potassium ion channels are involved in tumor generation and progression. Their over- and/or misexpression has been demonstrated in various tumors, and inhibition of these channels has suppressed proliferation of various cancer cells. We investigate and compare the pattern of expression of EAG and human ERG (HERG) channels in renal cell carcinoma and "normal" renal tissue.
Method:
Tissue samples, obtained at the time of radical nephrectomy from the tumor-bearing areas, and uninvolved renal tissue were preserved in 4% paraformaldehyde and cryosectioned at 20 mum. Immunohistochemical and Western blot analysis was performed on the tumor and uninvolved kidney parenchyma by incubating with polyclonal anti-HERG 1b (Alomone Lab, Israel), anti-EAG1, and anti-EAG2. Pattern of expression of EAG/HERG channels in normal renal tissue and carcinoma were noted and compared.
Results:
The study was performed on 16 radical and four partial nephrectomy specimens (n = 20). All tumors in the cohort were clear cell renal carcinoma. Normal renal tissue was found to exhibit heterogeneous cytoplasmic positivity for EAG1 and focal HERG immunoreactivity (IR) in the proximal (PCT) and distal convoluted tubules (DCT). EAG2 IR was absent in the normal renal tissue. Clear cell RCC demonstrated a loss of HERG expression while diffuse overexpression of EAG1 and EAG2 was noted. Western blot analysis corroborated the immunohistochemical observations.
Conclusions:
In our study both EAG1 and EAG2 potassium channels were overexpressed in clear cell renal cancer. In contrast to other adenocarcinomas, there is loss of HERG expression in clear cell RCC, which may possibly explain its chemoresistance. These ion channels may provide a potential for targeted therapy.
Insights
Ether-a-go-go (EAG) and EAG-related (ERG) potassium channels are implicated in cancer. This study found EAG1 and EAG2 channels overexpressed in clear cell renal cell carcinoma (RCC), while human ERG (HERG) expression was lost, suggesting potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Nephrology
Background:
- Voltage-gated potassium channels, including Ether-a-go-go (EAG) and EAG-related (ERG) subtypes, play roles in tumor development.
- Aberrant expression of these channels is observed in various cancers, and their inhibition can suppress cancer cell proliferation.
Purpose of the Study:
- To investigate and compare the expression patterns of EAG and human ERG (HERG) channels in clear cell renal cell carcinoma (RCC) and normal renal tissue.
- To assess the potential of these ion channels as therapeutic targets in RCC.
Main Methods:
- Immunohistochemical and Western blot analyses were performed on 20 renal tissue samples (16 radical, 4 partial nephrectomies).
- Tissue samples included tumor-bearing areas and uninvolved renal parenchyma.
- Antibodies against EAG1, EAG2, and HERG 1b were used to detect channel expression.
Main Results:
- Normal renal tissue showed heterogeneous cytoplasmic positivity for EAG1 and focal HERG immunoreactivity in tubules; EAG2 was absent.
- Clear cell RCC exhibited diffuse overexpression of EAG1 and EAG2.
- A significant loss of HERG expression was observed in clear cell RCC compared to normal tissue.
Conclusions:
- EAG1 and EAG2 potassium channels are overexpressed in clear cell renal cancer.
- Loss of HERG expression in clear cell RCC, unlike other adenocarcinomas, may contribute to chemoresistance.
- These ion channels represent potential targets for novel therapeutic strategies in renal cell carcinoma.
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