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Updated: Oct 13, 2026
Detection of G Protein-coupled Receptor Expression in Mouse Vagal Afferent Neurons using Multiplex In Situ Hybridization
Published on: September 20, 2021
Expression analysis of RET and the GDNF/GFRalpha-1 and NTN/GFRalpha-2 ligand complexes in pheochromocytomas and
E Edström1, T Frisk, F Farnebo
1Department of Surgery, Karolinska Hospital P9:03, SE-171 76 Stockholm, Sweden. Elisabeth.Edstrom@ks.se
Abstract:
Pheochromocytoma and its extra-adrenal counterpart paraganglioma are rare catecholamine producing tumors which usually occur sporadically but may also be a part of neuroendocrine tumor syndromes such as multiple endocrine neoplasia type 2A (MEN 2A). Activating mutations of the RET proto-oncogene which is the underlying cause of MEN 2A, is also seen in approximately 10% of sporadic pheochromocytomas. Glial cell line derived neurotrophic factor (GDNF) and neurturin (NTN) have been shown to function as independent ligands to RET, binding in a complex with the membrane-bound receptors GFRalpha-1 and GFRalpha-2 respectively. Here we have investigated the mRNA expression of RET and its ligand complexes, GDNF/GFRalpha-1 and NTN/GFRalpha-2, in a panel of pheochromocytomas and paragangliomas using mRNA in situ hybridization. RET expression was evident in normal adrenal medulla, and in 13/15 pheochromocytomas, including 5/5 MEN 2A associated tumors, but only in 1/10 paragangliomas. The frequent expression of RET in the pheochromocytomas suggest that this gene might be involved in the tumorigenesis. However, no expression of GDNF/GFRalpha-1 or NTN/GFRalpha-2 could be detected in any of the 25 tumors analyzed, suggesting that these ligand complexes are not important in the development of pheochromocytoma or paraganglioma.
Insights
RET proto-oncogene is frequently expressed in pheochromocytomas, suggesting a role in tumor development. However, its ligands, GDNF/GFRalpha-1 and NTN/GFRalpha-2, were not detected, indicating they are not crucial for these rare neuroendocrine tumors.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Pheochromocytoma and paraganglioma are rare neuroendocrine tumors producing catecholamines.
- RET proto-oncogene mutations cause Multiple Endocrine Neoplasia type 2A (MEN 2A) and are found in sporadic pheochromocytomas.
- RET acts as a receptor for Glial cell line derived neurotrophic factor (GDNF) and Neurturin (NTN).
Purpose of the Study:
- To investigate the mRNA expression of RET and its ligand complexes (GDNF/GFRalpha-1, NTN/GFRalpha-2) in pheochromocytomas and paragangliomas.
- To determine the potential role of RET signaling in the tumorigenesis of these rare tumors.
Main Methods:
- mRNA in situ hybridization was used to analyze gene expression.
- A panel of pheochromocytomas and paragangliomas were examined.
- Normal adrenal medulla tissue was included as a control.
Main Results:
- RET mRNA expression was detected in normal adrenal medulla and in most pheochromocytomas (13/15), including MEN 2A-associated tumors (5/5).
- RET expression was infrequent in paragangliomas (1/10).
- No expression of GDNF/GFRalpha-1 or NTN/GFRalpha-2 ligand complexes was found in any of the 25 tumors analyzed.
Conclusions:
- Frequent RET expression in pheochromocytomas suggests its involvement in tumorigenesis.
- The lack of GDNF/GFRalpha-1 and NTN/GFRalpha-2 expression indicates these specific ligand complexes are not critical for pheochromocytoma or paraganglioma development.
