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Angiotensin-2 receptors (AT1-R and AT2-R), new prognostic factors for renal clear-cell carcinoma?
T Dolley-Hitze1, F Jouan, B Martin
1CNRS UMR6061/IFR140, Faculté de Médecine Université de Rennes 1, 2 avenue du professeur Léon Bernard, CS34317, 35043 Rennes Cedex, France.
Background:
The growth factor Angiotensin-2 signals through Angiotensin receptor type 1 (AT1-R) in a broad range of cell types and tumours and through the type-2 receptor (AT2-R) in a more restricted group of cell types. Although numerous forms of cancer have been shown to overexpress AT1-R, expression of AT1-R and AT2-R by human renal clear-cell carcinoma (RCCC) is not well understood. In this study, the expression of both angiotensin receptors was quantified in a retrospective series of RCCC and correlated with prognostic factors.
Methods:
Angiotensin receptor type 1 and AT2-R expressions were quantified on tumour tissues by immunohistochemistry (IHC), western blot and quantitative reverse transcriptase PCR (qRT-PCR). IHC results were correlated to Fuhrman's grade and patient progression-free survival (PFS).
Results:
A total of 84 RCCC were analysed. By IHC, AT1-R and AT2-R were expressed to a greater level in high-grade tumours (AT1-R: P<0.001, AT2-R: P<0.001). Univariate analysis showed a correlation between PFS and AT1-R or AT2-R expression (P=0.001). By multivariate analysis, only AT2-R expression correlated with PFS (HR 1.021, P=0.006) and cancer stage (P<0.001). By western blot, AT1-R and AT1-R were also found to be overexpressed in higher Fuhrman's grade (P<0.01 and P=0.001 respectively). By qRT-PCR, AT1-R but not AT2-R mRNA were downregulated (P=0.001 and P=0.118, respectively).
Conclusion:
Our results show that AT1-R and AT2-R proteins are overexpressed in the most aggressive forms of RCCC and that AT2-R expression correlates with PFS. AT1-R or AT2-R blockage could, therefore, offer novel directions for anti-RCCC therapy.
Insights
Angiotensin receptors type 1 and 2 (AT1-R and AT2-R) are overexpressed in aggressive human renal clear-cell carcinoma (RCCC). AT2-R expression specifically correlates with progression-free survival, suggesting potential therapeutic targets for RCCC.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Angiotensin-2 signaling involves AT1-R and AT2-R, impacting various cells and tumors.
- AT1-R is overexpressed in many cancers, but AT1-R and AT2-R expression in human renal clear-cell carcinoma (RCCC) remains unclear.
Purpose of the Study:
- To quantify AT1-R and AT2-R expression in RCCC.
- To correlate receptor expression with prognostic factors like tumor grade and patient survival.
Main Methods:
- Immunohistochemistry (IHC), western blot, and qRT-PCR were used to quantify AT1-R and AT2-R expression in 84 RCCC tissues.
- IHC results were correlated with Fuhrman's grade and progression-free survival (PFS).
Main Results:
- AT1-R and AT2-R proteins were significantly overexpressed in high-grade RCCC (P<0.001).
- Both AT1-R and AT2-R expression correlated with PFS in univariate analysis (P=0.001).
- Multivariate analysis revealed AT2-R expression as an independent predictor of PFS (P=0.006) and cancer stage (P<0.001). AT1-R mRNA was downregulated (P=0.001).
Conclusions:
- AT1-R and AT2-R proteins are upregulated in aggressive RCCC.
- AT2-R expression is a significant prognostic marker for PFS in RCCC patients.
- Targeting AT1-R or AT2-R may offer new therapeutic strategies for RCCC.
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