title: Activation of GPR54 promotes cell cycle arrest and apoptosis of human tumor cells through a specific transcriptional program not shared by other Gq-coupled receptors.
abstract: GPR54 is a receptor for peptides derived from the metastasis suppressor gene KiSS-1. To investigate the intracellular mechanisms involved in the reduction of the metastatic potential of MDA-MB-435S cells expressing GPR54, a time course stimulation by kisspeptin-10 over a period of 25 h was performed using cDNA microarrays. Comparison with the bradykinin B(2) receptor revealed a distinct pattern of gene regulation despite a common coupling to the G(q/11) class of G-proteins. Inhibitors of PLC and PK-C abolished the transcriptional regulation of all tested genes, while an inhibitor of p42/44 affected a subset of genes controlled both by GPR54 and B(2). Among the genes specifically up-regulated by GPR54, we found several proapoptotic genes. Stimulation of GPR54 promoted apoptosis while no significant change was observed after B(2) receptor activation. Our results suggest that the metastasis suppressor properties of GPR54 are mediated in part by cell cycle arrest and induction of apoptosis in malignant cells.
authors.affiliation: Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Campus Erasme, Route de Lennik 808, B-1070 Brussels, Belgium.
authors.forename: Jérôme A J
authors.initials: JA
authors.lastname: Becker
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mirjolet
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bernard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Burgeon
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Simons
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vassart
authors.forename: Marc
authors.initials: M
authors.lastname: Parmentier
authors.forename: Frédérick
authors.initials: F
authors.lastname: Libert
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: C118688:KISS1R protein, human; D043782:Receptor, Bradykinin B2; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide