title: The activation of type 1 corticotropin releasing factor receptor (CRF-R1) inhibits proliferation and promotes differentiation of neuroblastoma cells in vitro via p27(Kip1) protein up-regulation and c-Myc mRNA down-regulation.
abstract: Our group has previously shown that corticotropin releasing factor (CRF) inhibits proliferation of human endocrine-related cancer cell lines via the activation of CRF type-1 receptors (CRF-R1). Tumors originating from the nervous system also express CRF receptors but their role on neoplastic cell proliferation was poorly investigated. Here we investigated the effect of CRF receptor stimulation on nervous system-derived cancer cells, using the SK-N-SH (N) human neuroblastoma cell line as an experimental model. We found that SK-N-SH (N) cells express functionally active CRF-R1, whose activation by CRF and the cognate peptide urocortin (UCN) is associated to reduced cell proliferation and motility, as well as neuronal-like differentiation. UCN did not interfere with cell viability and cell-cycle arrest. Those effects seem to be mediated by a mechanism involving the activation of cAMP/PKA/CREB pathway and the subsequent downstream increase in p27(Kip1) and underphosphorylated retinoblastoma protein levels, as well as reduced c-Myc mRNA accumulation.
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy. Electronic address: giacomopozzoli@rm.unicatt.it.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Pozzoli
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: De Simone
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Cantalupo
authors.affiliation: Institute of Translational Pharmacology, National Research Council, Via Fosso del Cavaliere 100, 00133, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cenciarelli
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Lisi
authors.affiliation: "Giovanni XXIII" Cancer Research Center - Institute of General Pathology, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Alma
authors.initials: A
authors.lastname: Boninsegna
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Dello Russo
authors.affiliation: "Giovanni XXIII" Cancer Research Center - Institute of General Pathology, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sgambato
authors.affiliation: Institute of Pharmacology, Catholic University School of Medicine, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Navarra
mesh_terms: D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009447:Neuroblastoma; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D054832:Urocortins / Q000502:physiology; D000099052:CRF Receptor, Type 1
chemical_list: C436291:CDKN1B protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D018019:Receptors, Corticotropin-Releasing Hormone; D016160:Retinoblastoma Protein; D054832:Urocortins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone
keywords: CREB; Corticotropin releasing factor; Neuroblastoma; Retinoblastoma (Rb) protein; Urocortin; c-Myc