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Updated: Aug 7, 2026
The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma
Meaghan L Douglas1, Michelle M Richardson, David L Nicol
1Southern Clinical Division, School of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Background:
The endothelin axis has been implicated in cancer growth, angiogenesis, and metastasis, but to the authors' knowledge the expression of endothelin genes has not been defined in renal cell carcinoma (RCC).
Methods:
Tissue specimens were harvested from both normal and tumor-affected regions at the time of radical nephrectomy from 35 patients with RCC (22 with clear cell RCC [ccRCC] and 13 with papillary RCC [PRCC]). Real-time reverse transcriptase-polymerase chain reaction analysis determined the expression profile of the preproendothelins (PPET-1, PPET-2, and PPET-3), the endothelin receptors (ET(A) and ET(B)), and the endothelin-converting enzymes (ECE-1 and ECE-2).
Results:
PPET-1 was found to be up-regulated in ccRCC tumor specimens and down-regulated in PRCC tumor specimens. ET(A) was significantly down-regulated in PRCC tumor specimens. ECE-1 was expressed in all tissue specimens at comparable levels, with moderate but significant elevation in normal tissue specimens associated with PRCC. Of the other genes, PPET-2 and ET(B) were expressed in all tissue specimens and no differences were observed between tumor subtypes or tumor-affected and normal tissue specimens, whereas PPET-3 and ECE-2 were present in all tissue specimens but were barely detectable.
Conclusions:
The endothelin axis was expressed differently in the two main subtypes of RCC and appeared to match macroscopic features commonly observed in these tumors (i.e., high expression of PPET-1 in hypervascular ccRCC contrasted against low PPET-1 and ET(A) expression in hypovascular PRCC). The presence of ECE-1 mRNA in these tissue specimens suggested that active endothelin ligands were present, indicating endothelin axis activity was elevated in ccRCC compared with normal kidney, but impaired in PRCC. The current study provided further evidence that it is not appropriate to consider ccRCC and PRCC indiscriminately in regard to treatment.
Insights
The endothelin axis shows distinct expression patterns in clear cell (ccRCC) and papillary renal cell carcinoma (PRCC). This suggests different treatment approaches are needed for these renal cell carcinoma subtypes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The endothelin signaling pathway is implicated in various cancers.
- Gene expression of the endothelin axis in renal cell carcinoma (RCC) subtypes remains underexplored.
Purpose of the Study:
- To investigate the expression profiles of key endothelin axis genes in clear cell RCC (ccRCC) and papillary RCC (PRCC).
- To determine if differential gene expression correlates with known clinicopathological features of RCC subtypes.
Main Methods:
- Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze gene expression.
- Tissue specimens from 35 RCC patients (22 ccRCC, 13 PRCC) were analyzed.
- Expression of preproendothelins (PPET-1, PPET-2, PPET-3), endothelin receptors (ET(A), ET(B)), and endothelin-converting enzymes (ECE-1, ECE-2) was quantified.
Main Results:
- PPET-1 was upregulated in ccRCC and downregulated in PRCC.
- ET(A) was significantly downregulated in PRCC.
- ECE-1 was ubiquitously expressed, with higher levels in normal kidney tissue adjacent to PRCC.
Conclusions:
- Differential expression of the endothelin axis in ccRCC and PRCC correlates with tumor vascularity.
- Elevated endothelin axis activity in ccRCC and impaired activity in PRCC were suggested.
- Findings support distinct therapeutic strategies for ccRCC and PRCC.
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