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Published on: July 3, 2015
A delta opioid receptor lacking the third cytoplasmic loop is generated by atypical mRNA processing in human
P Mayer1, H Tischmeyer, M Jayasinghe
1Institute for Pharmacology and Toxicology, Otto von Guericke University of Magdeburg, Germany.
Abstract:
delta Opioid receptors were identified in human melanomas by RT-PCR and radioligand binding. In all tumors an additional PCR amplificate was detected in which 144 bp within the third exon were deleted. This fragment corresponded to the third cytoplasmic domain of the receptor protein. The short variant resulted from atypical mRNA processing. There were no common splice recognition sequences around the deleted fragment; instead its excision resembled the removal of a transposon. The deletion was not detected in normal human melanocytes nor in human or rat brain. However, it was present in a human neuroblastoma cell line (SH-SY5Y). Thus, it appears that the occurrence of the short delta opioid receptor is correlated to malignancy.
Insights
Researchers found a shorter delta opioid receptor variant in human melanomas, likely linked to cancer. This variant, absent in healthy cells, suggests a correlation between the altered receptor and malignancy.
Area of Science:
- Molecular biology
- Oncology
- Neuroscience
Background:
- Delta opioid receptors (DOR) are G protein-coupled receptors involved in various physiological processes.
- Aberrant receptor expression and function are implicated in cancer development and progression.
Purpose of the Study:
- To investigate the presence and characteristics of delta opioid receptors in human melanomas.
- To determine if specific DOR variants are associated with melanoma malignancy.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) to detect DOR mRNA.
- Radioligand binding assays to quantify DORs.
- Analysis of mRNA processing and splice variants.
Main Results:
- Delta opioid receptors were identified in human melanomas.
- A shorter DOR variant, lacking 144 bp from the third exon (third cytoplasmic domain), was consistently detected in all tumors.
- This variant resulted from atypical mRNA processing, resembling transposon excision, and was absent in normal melanocytes and brain tissue.
- The short DOR variant was also found in a human neuroblastoma cell line.
Conclusions:
- The short delta opioid receptor variant appears to be specifically associated with malignancy.
- Its unique processing suggests a potential role in melanoma development or progression.
- Further research is warranted to elucidate the functional implications of this variant in cancer.
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