Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of monoamine transporters in neuroblastoma cell lines: correlations to meta-iodobenzylguanidine (MIBG) uptake and tyrosine hydroxylase gene expression.
Radiolabelled meta-iodobenzylguanidine (MIBG) has been widely used in scintigraphy and targeted radiotherapy in patients with neuroblastoma. Recently, it has been demonstrated that MIBG is incorporated into neuroblastoma cells by the noradrenaline transporter. In vitro experiments on SK-N-SH human neuroblastoma cells performed in the present study showed that uptake of MIBG is inhibited by noradrenaline, more so by dopamine and to a lesser extent, by serotonin, indicating that the respective transporters may also contribute to MIBG uptake. However, neither dopamine nor serotonin transporter gene expression was detected. Noradrenaline transporter gene expression was found in 4 of 6 investigated cell lines, which correlated with specific MIBG uptake. Furthermore, an inverse correlation of noradrenaline transporter and tyrosine hydroxylase gene expression, the key regulatory enzyme of catecholamine synthesis, was observed. These data show that MIBG is specifically incorporated only in neuroblastoma cells in which there is noradrenaline transporter gene expression. Furthermore, the catecholamine status in neuroblastoma cells is regulated by a coordinate expression of the key elements of catecholamine synthesis and reuptake systems.
Lode
H N
HN
Children's Hospital, University of Tübingen, Germany.
Bruchelt
G
G
Seitz
G
G
Gebhardt
S
S
Gekeler
V
V
Niethammer
D
D
Beck
J
J
D019797:3-Iodobenzylguanidine; D001483:Base Sequence; D015306:Biogenic Monoamines / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007462:Iodobenzenes / Q000493:pharmacokinetics*; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D016133:Polymerase Chain Reaction; D027981:Symporters; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
D015306:Biogenic Monoamines; D002352:Carrier Proteins; D007462:Iodobenzenes; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D027981:Symporters; D019797:3-Iodobenzylguanidine; D014446:Tyrosine 3-Monooxygenase