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Immunolocalization of the AT-1R Ang II Receptor in Human Kidney Cancer
Antonella Muscella1, Leonardo Resta2, Luca Giulio Cossa1
1Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.), Università del Salento, Via Provinciale per Monteroni, 73100 Lecce, Italy.
Abstract:
This study aimed to evaluate AT1-R expression in normal and cancerous human kidneys, how these expressions are modified, and AT1-R functionality. AT-1R mRNA expression, determined by real-time PCR, was detected in all samples. AT-1R mRNA increased in well-differentiated cancer (G1, p < 0.01) and decreased 2.9-fold in undifferentiated cancer (G4, p < 0.001) compared with normal kidney tissues. Immunocytochemistry analysis showed that the AT-1R was expressed in the normal tubular epithelium. The glomerulus was also immunoreactive, and as expected, the smooth muscle cells of the vessel walls also expressed the receptor. A total of 35 out of 42 tumors were AT-1R positive, with the cell tumors showing varying numbers of immunoreactive cells, which were stained in a diffuse cytoplasmic and membranous pattern. Computer-assisted counting of the stained tumor cells showed that the number of AT-1R-positive cells increased in the well-differentiated cancers. The functionality of AT-1R was assessed in primary cultures of kidney epithelial cells obtained from three G3 kidney cancer tissues and corresponding histologically proven non-malignant tissue adjacent to the tumor. Indeed, Ang II stimulated, in a dose-dependent manner, the 24 h proliferation of normal kidney cells and cancer cells in the primary culture and phosphorylated extracellular regulated kinases 1 and 2. In conclusion, Ang II may be involved in the growth or function of neoplastic kidney tissue.
Insights
Angiotensin II receptor type 1 (AT1-R) expression varies in kidney cancer, increasing in well-differentiated tumors and decreasing in undifferentiated ones. Angiotensin II may influence kidney tumor growth and function.
Area of Science:
- Nephrology
- Oncology
- Molecular Biology
Background:
- The renin-angiotensin system plays a role in kidney physiology.
- Angiotensin II receptor type 1 (AT1-R) is a key component of this system.
- Understanding AT1-R in kidney cancer is crucial for potential therapeutic targets.
Purpose of the Study:
- To investigate AT1-R expression levels in normal and cancerous human kidney tissues.
- To analyze modifications in AT1-R expression during kidney cancer progression.
- To assess the functional role of AT1-R in kidney epithelial cells and tumors.
Main Methods:
- Real-time PCR for AT1-R mRNA quantification.
- Immunocytochemistry for AT1-R protein localization and expression.
- Primary cell culture of kidney epithelial cells for functional assays.
- Assessment of cell proliferation and extracellular signal-regulated kinases (ERK) phosphorylation.
Main Results:
- AT1-R mRNA was detected in all kidney samples.
- AT1-R mRNA levels increased in well-differentiated (G1) and decreased in undifferentiated (G4) kidney cancers compared to normal tissue.
- AT1-R protein was found in normal tubular epithelium, glomeruli, vessel walls, and kidney tumors, with higher expression in well-differentiated cancers.
- Angiotensin II stimulated proliferation and ERK phosphorylation in normal and cancerous kidney epithelial cells in a dose-dependent manner.
Conclusions:
- AT1-R expression is altered in kidney cancer, correlating with differentiation status.
- The AT1-R is functionally active in kidney epithelial cells, responding to Angiotensin II.
- Angiotensin II may play a role in the growth and function of neoplastic kidney tissue, suggesting AT1-R as a potential therapeutic target.
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