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Accueil > Bibliographie > Expression of somatostatin receptors, dopamine D2 receptors, noradrenaline (...)

Expression of somatostatin receptors, dopamine D2 (...)

Endocr Relat Cancer. 2011 Apr ;18(2):287-300
Expression of somatostatin receptors, dopamine D2 receptors, noradrenaline transporters and vesicular monoamine transporters in 52 pheochromocytomas and paragangliomas.
Saveanu A, Muresan M, De Micco C, Taieb D, Germanetti AL, Sebag F, Henry JF, Brunaud L, Enjalbert A, Weryha G, Barlier A.

While somatostatin receptors (sst), through somatostatin radiolabeled analogs, are used, mainly in second line, in the diagnosis and treatment of pheochromocytomas(PCC) and paragangliomas(PGL), the clinical significance of dopamine receptor type 2(D2DR) in PCC/PGL is unknown. Indeed, radiolabeled dopamine (DA) analogs such as fluorine18 (18F)-DA, used for positron emission tomography in PCC localization, are mainly correlated to the presence of noradrenalin transporter(NET) and vesicular monoamine transporters(VMAT) but not to D2DR. The aim of this study was to quantitate D2DR and sst expression in 52 PCC/PGL and to compare it with that of 35 gastroenteropancreatic-neuroendocrine(GEP-NE) tumors. Quantitative RT-PCR analysis of sst1-3 and 5, D2DR, NET, VMAT1/2 mRNA. Immunohistochemistry analysis of sst2 and D2DR was performed in 7 tumors. Results : D2DR mRNA was expressed in all PCC/PGL. Mean expression was significantly higher than in GEP-NE tumors (4.8 vs 0.5 copy/copy β-Gus). Sst2 and sst1 were expressed in most PCC/PGL, with sst2 dominant expression (mean mRNA : 1.6 vs 0.4 copy/copy β-Gus). Sst2 expression level was similar to that of GEP-NE tumors, whereas sst5 expression level was significantly lower (0.12 vs 0.78 copy/copy β-Gus). Conclusion : Our study evidenced strong D2DR mRNA expression in PCC and for the first time in PGL. PCC/PGL express sst2 mRNA at levels similar to those of GEP-NE tumors. New drugs can target ssts and D2DR more efficiently than current somatostatin analogs. Moreover, transporters like NET and VMAT1/2, could be cotargeted with sst, as a basis of new radionuclide compounds in the imaging and treatment of these tumors.

PubMed

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