Insulin-like growth factor binding protein 5: contribution to growth and differentiation of neuroblastoma cells

Autor: Roberta Vitali, Giuseppe Raschellà, Fabiola Sesti, Barbara Tanno, Camillo Mancini, Vincenzo Cesi, Maria Laura Giuffrida
Rok vydání: 2005
Předmět:
medicine.medical_specialty
medicine.medical_treatment
Blotting
Western
Retinoic acid
Mitosis
Tretinoin
Transfection
General Biochemistry
Genetics and Molecular Biology
Insulin-like growth factor-binding protein
Paracrine signalling
chemistry.chemical_compound
Neuroblastoma
History and Philosophy of Science
Insulin-Like Growth Factor II
Internal medicine
Cell Line
Tumor
medicine
Humans
Autocrine signalling
Luciferases
Promoter Regions
Genetic
Cell Proliferation
DNA Primers
biology
Dose-Response Relationship
Drug
Models
Genetic
Cell growth
Reverse Transcriptase Polymerase Chain Reaction
General Neuroscience
Binding protein
Growth factor
Cell Differentiation
Recombinant Proteins
Cell biology
Endocrinology
Phenotype
chemistry
Mutation
biology.protein
Signal transduction
Insulin-Like Growth Factor Binding Protein 5
Plasmids
Signal Transduction
Zdroj: Annals of the New York Academy of Sciences. 1028
ISSN: 0077-8923
Popis: Neuroblastoma (NB) is a childhood tumor that depends on insulin-like growth factors (IGFs) for its growth and metastatic spread. Some metastatic NBs acquire independence from the paracrine support of IGF by activating autocrine production of IGF-2. Insulin-like growth factor binding protein-5 (IGFBP-5), a member of the IGF binding protein family, is able to optimize binding between IGF itself and its receptor. NB cell lines retain the ability to differentiate in vitro toward neuronal, schwann-like or melanocytic phenotypes upon treatment with retinoic acid (RA). Retinoids are currently used in NB therapy to achieve a mature postmitotic phenotype. Here, we present evidence that the expression of IGFBP-5 is a common feature of neuroblastoma cell lines and that IGFBP-5 acts in concert with IGF-2 in inducing cell proliferation. RA-induced differentiation causes a sharp increase of IGFBP-5. Functional assays carried out in differentiating conditions demonstrate that IGFBP-5 transcription is sensitive to RA treatment. We show that the effect of RA on the IGFBP-5 promoter is exerted, at least in part, through a proximal 5′-CACCC-3′ tandem repeat (−147 bp to −137 bp from the transcription start site) that has previously been described as a cis-acting element involved in the progesterone-mediated response in osteoblasts. Given the relevance of IGF-2 in determining the proliferative and metastatic behavior of NB, the role of IGFBP-5 as a modulator of the IGF signal transduction pathway should be studied further for potential therapeutic applications.
Databáze: OpenAIRE
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