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D1 dopamine receptors are not expressed in human melanoma
R Böni1, W Lichtensteiger, H C Steinert
1Department of Dermatology, University Hospital of Zürich, Switzerland.
Abstract:
D1 dopamine receptor mRNA has been demonstrated in mouse melanoma cells, and the expression of these G-protein-coupled receptors in human melanoma was therefore presumed when dopamine receptor binding radiopharmaceuticals were found to be useful for the detection of metastases in whole-body scintigraphy. The aim of this study was thus to investigate if D1 dopamine receptor mRNA or protein could be directly demonstrated in melanoma cells. The presence of D1 dopamine receptor mRNA was investigated in six human melanoma cell lines from metastases using reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, in vitro binding assays with the D1 dopamine receptor agonist 125I-Sch 23982 were performed in 19 melanoma metastases. No D1 dopamine receptor mRNA could be detected by RT-PCR. All melanotic metastases were found to accumulate 125I-Sch 23982, with the presence of binding sites and intensity of 125I-Sch 23982 labelling correlating to the amount of melanin present in the metastases. Two amelanotic melanomas did not accumulate 125I-Sch 23982. D1 dopamine receptors could not be detected by means of RT-PCR or in vitro binding assays in human melanomas. Detection of antagonists is best explained by non-specific binding to melanin.
Insights
This study found no D1 dopamine receptors in human melanoma cells. The radiotracer accumulation observed in melanotic melanoma metastases is likely due to non-specific melanin binding, not receptor interaction.
Area of Science:
- Oncology
- Molecular Biology
- Radiopharmaceuticals
Background:
- Dopamine receptors are G-protein-coupled receptors.
- D1 dopamine receptor mRNA has been found in mouse melanoma cells.
- Radiopharmaceuticals targeting dopamine receptors have shown utility in detecting melanoma metastases.
Purpose of the Study:
- To investigate the presence of D1 dopamine receptor mRNA and protein in human melanoma.
- To determine if D1 dopamine receptors are directly expressed in human melanoma cells.
Main Methods:
- Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect D1 dopamine receptor mRNA in six human melanoma cell lines.
- In vitro binding assays with the D1 dopamine receptor agonist 125I-Sch 23982 were performed on 19 melanoma metastases.
Main Results:
- D1 dopamine receptor mRNA was not detected in any of the tested human melanoma cell lines via RT-PCR.
- All melanotic melanoma metastases showed accumulation of 125I-Sch 23982.
- The accumulation of 125I-Sch 23982 correlated with melanin content, and two amelanotic melanomas did not accumulate the radiotracer.
- D1 dopamine receptors were not detected in human melanomas by RT-PCR or in vitro binding assays.
Conclusions:
- D1 dopamine receptors are not expressed in human melanoma cells.
- The observed binding of radiopharmaceuticals in melanotic melanoma is attributed to non-specific binding to melanin, not D1 dopamine receptor expression.
- Current radiopharmaceuticals used for melanoma metastasis detection may not be specific to D1 dopamine receptors.