title: Expression and down-regulation by retinoic acid of IGF binding protein-2 and -4 in medium from human neuroblastoma cells.
abstract: Insulin-like growth factors (IGFs) regulate the autocrine/paracrine growth of neuroblastomas. The IGFs bind to specific binding proteins (IGFBPs) which modulate their biological activity. We investigated, by Western ligand blotting (WLB), the presence of IGFBPs and their possible modulation by retinoic acid (RA), IGF-I, IGF-II and truncated Des(1-3)IGF-I in conditioned medium (CM) of the human neuroblastoma SK-N-BE(2) cell line. We demonstrated the presence of two IGFBPs, with MW 37 kDa and 25 kDa. Following immunoprecipitation, they turned out to be IGFBP-2 and -4, respectively. The RA-induced differentiation in SK-N-BE(2) cells was accompanied by a marked reduction of the intensity of both IGFBP bands after 48 h (32% and 24% of control, respectively) and 72 h (2% and 0% of control, respectively) incubation. The addition of exogenous IGFs, which did not induce cell differentiation, did not change the IGFBP pattern significantly, except for the truncated form of IGF-I, which induced a marked decrease in both the 37 kDa and 25 kDa bands after 72 h incubation (45% and 18% of control, respectively). These findings suggest that IGFBPs have a role in RA-induced differentiation in human neuroblastoma cells.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bernardini
authors.forename: S
authors.initials: S
authors.lastname: Cianfarani
authors.forename: A
authors.initials: A
authors.lastname: Spagnoli
authors.forename: M
authors.initials: M
authors.lastname: Annicchiarico-Petruzzelli
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.forename: R
authors.initials: R
authors.lastname: Massoud
authors.forename: B
authors.initials: B
authors.lastname: Boscherini
authors.forename: A
authors.initials: A
authors.lastname: Finazzi-Agró
authors.forename: R G
authors.initials: RG
authors.lastname: Rosenfeld
authors.forename: G
authors.initials: G
authors.lastname: Federici
mesh_terms: D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D007163:Immunosorbent Techniques; D018971:Insulin-Like Growth Factor Binding Protein 2; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D016501:Neurites / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism* / Q000648:ultrastructure; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D014212:Tretinoin