title: Genetic and Functional Analysis of Polymorphisms in the Human Dopamine Receptor and Transporter Genes in Small Cell Lung Cancer.
abstract: The regulatory role of dopamine (DA) in endocrine, cardiovascular and renal functions has been extensively studied and used for clinical purposes. More recently DA has been indicated as a regulatory molecule for immune cells and malignant cell proliferation. We assessed the expression and the functional role DA, DA receptors, and transporters in primary small cell lung cancer (SCLC). By HPLC DA plasma levels were more elevated in SCLC patients in comparison with NSCLC patients and healthy controls. SCLC cell expressed DA D1- and D2-like receptors and membrane and vesicular transporters at protein and mRNA levels. We also investigated the effects of independent D1- or D2-like receptor stimulation on SCLC cell cultures. DA D1 receptor agonist SKF38393 induced the increase of cAMP levels and DARPP-32 protein expression without affecting SCLC growth rate. Cell treatment with the DA D1 receptor antagonist SCH23390 inhibited SKF38393 effects. In contrast, the DA D2 receptor agonist quinpirole (10 μM) counteracted, in a dose and time dependent way, SCLC cell proliferation, it did not affect cAMP levels and decreased phosphorylated AKT that was induced by DA D2 receptor antagonist sulpiride. However, in only one SCLC line, stimulation of DA D2 receptor failed to inhibit cell proliferation in vitro. This effect was associated to the existence of rs6275 and rs6277 polymorphisms in the D2 gene. These results gave more insight into DA control of lung cancer cell behavior and suggested the existence of different SCLC phenotypes.
authors.affiliation: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cherubini
authors.affiliation: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Di Napoli
authors.affiliation: Dipartimento di Chirurgia Pietro Valdoni, Sapienza Università di Roma, Rome, Italy.|IRCCS Istituto Nazionale Tumori, Fondazione G. Pascale, Napoli, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Noto
authors.affiliation: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy.
authors.forename: Giorgia Amira
authors.initials: GA
authors.lastname: Osman
authors.affiliation: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Esposito
authors.affiliation: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mariotta
authors.affiliation: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Sellitri
authors.affiliation: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ruco
authors.affiliation: Chirurgia Toracica Ospedale San Camillo-Forlanini, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cardillo
authors.affiliation: IRCCS Istituto Nazionale Tumori, Fondazione G. Pascale, Napoli, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.affiliation: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy.|Dipartimento di Chirurgia Pietro Valdoni, Sapienza Università di Roma, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Mancini
authors.affiliation: Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ricci
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D004298:Dopamine / Q000097:blood; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011954:Receptors, Dopamine / Q000235:genetics* / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000378:metabolism*
chemical_list: C581293:DRD2 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497928:PPP1R1B protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000262:Adenylyl Cyclases; D004298:Dopamine