PMID- 21335363 OWN - NLM STAT- MEDLINE DCOM- 20120227 LR - 20110322 IS - 1479-6821 (Electronic) IS - 1351-0088 (Linking) VI - 18 IP - 2 DP - 2011 Apr TI - Expression of somatostatin receptors, dopamine D(2) receptors, noradrenaline transporters, and vesicular monoamine transporters in 52 pheochromocytomas and paragangliomas. PG - 287-300 LID - 10.1530/ERC-10-0175 [doi] AB - 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 subtype 2 (D(2)) in PCC/PGL is unknown. Indeed, radiolabeled dopamine (DA) analogs such as fluorine 18 ((18)F)-DA, used for positron emission tomography in PCC localization, are mainly correlated to the presence of noradrenaline transporter (NAT) and vesicular monoamine transporters (VMAT) but not to D(2). The aim of this study was to quantitate D(2) and sst expression in 52 PCC/PGL and to compare it with that of 35 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Quantitative RT-PCR of sst(1-3) and sst(5), D(2), NAT, VMAT1/2 was performed in all tumors, while immunohistochemistry analysis of sst(2) and D(2) was performed in seven tumors. D(2) mRNA was expressed in all PCC/PGL. Mean expression was significantly higher in PCC/PGL than in GEP-NETs (4.8 vs 0.5 copy/copy beta-glucuronidase (Gus)). sst(2) and sst(1) were expressed in most PCC/PGL, with sst(2)-dominant expression (mean mRNA: 1.6 vs 0.4 copy/copy beta-Gus). sst(2) expression level was similar to that of GEP-NETs, whereas sst(5) expression level was significantly lower (0.12 vs 0.78 copy/copy beta-Gus). Our study evidenced strong D(2) mRNA expression in PCC and for the first time in PGL. PCC/PGL express sst(2) mRNA at levels similar to those of GEP-NETs. New drugs can target ssts and D(2) more efficiently than current somatostatin analogs. Moreover, transporters like NAT and VMAT1/2, could be co-targeted with sst, as a basis of new radionuclide compounds in the imaging and treatment of these tumors. FAU - Saveanu, Alexandru AU - Saveanu A AD - Laboratory of Biochemistry and Molecular Biology, Centre Hospitalo-Universitaire Conception, 147 Boulevard Baille, 13385 Marseille, France. FAU - Muresan, Mihaela AU - Muresan M FAU - De Micco, Catherine AU - De Micco C FAU - Taieb, David AU - Taieb D FAU - Germanetti, Anne-Laure AU - Germanetti AL FAU - Sebag, Frederic AU - Sebag F FAU - Henry, Jean-Francois AU - Henry JF FAU - Brunaud, Laurent AU - Brunaud L FAU - Enjalbert, Alain AU - Enjalbert A FAU - Weryha, Georges AU - Weryha G FAU - Barlier, Anne AU - Barlier A LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110321 PL - England TA - Endocr Relat Cancer JT - Endocrine-related cancer JID - 9436481 RN - 0 (Norepinephrine Plasma Membrane Transport Proteins) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Dopamine D2) RN - 0 (Receptors, Somatostatin) RN - 0 (SLC18A1 protein, human) RN - 0 (SLC18A2 protein, human) RN - 0 (Vesicular Monoamine Transport Proteins) SB - IM MH - Adolescent MH - Adrenal Gland Neoplasms/metabolism MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Norepinephrine Plasma Membrane Transport Proteins/genetics/*metabolism MH - Pancreatic Neoplasms/metabolism MH - Paraganglioma/*metabolism MH - Pheochromocytoma/*metabolism MH - RNA, Messenger/metabolism MH - Real-Time Polymerase Chain Reaction MH - Receptors, Dopamine D2/genetics/*metabolism MH - Receptors, Somatostatin/genetics/*metabolism MH - Vesicular Monoamine Transport Proteins/genetics/*metabolism MH - Young Adult EDAT- 2011/02/22 06:00 MHDA- 2012/03/01 06:00 CRDT- 2011/02/22 06:00 PHST- 2011/02/22 06:00 [entrez] PHST- 2011/02/22 06:00 [pubmed] PHST- 2012/03/01 06:00 [medline] AID - ERC-10-0175 [pii] AID - 10.1530/ERC-10-0175 [doi] PST - epublish SO - Endocr Relat Cancer. 2011 Mar 21;18(2):287-300. doi: 10.1530/ERC-10-0175. Print 2011 Apr.