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Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma therapy

LU, C ; EVERHART, L ; ABE, K ; ZUKOWSKA, Z ; TORETSKY, J. A ; KITLINSKA, J ; TILAN, J ; KUO, L ; SUN, C-Cj ; MUNIVENKATAPPA, R. B ; JÖNSSON-RYLANDER, A.-C ; SUN, J ; KUAN-CELARIER, A ; LI, L

Oncogene, 2010-10, Vol.29 (41), p.5630-5642 [Periódico revisado por pares]

Basingstoke: Nature Publishing Group

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Título:
Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma therapy
Autor: LU, C ; EVERHART, L ; ABE, K ; ZUKOWSKA, Z ; TORETSKY, J. A ; KITLINSKA, J ; TILAN, J ; KUO, L ; SUN, C-Cj ; MUNIVENKATAPPA, R. B ; JÖNSSON-RYLANDER, A.-C ; SUN, J ; KUAN-CELARIER, A ; LI, L
Assuntos: Angiogenesis ; Animals ; Apoptosis ; Apoptosis - drug effects ; Arginine - analogs & derivatives ; Arginine - pharmacology ; Benzazepines - pharmacology ; BIM protein ; Biological and medical sciences ; Blotting, Western ; Cancer ; Care and treatment ; Cell Line ; Cell Line, Tumor ; Cell physiology ; Cell proliferation ; Cell Proliferation - drug effects ; Cell receptors ; Cell structures and functions ; Cell Survival - drug effects ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; DNA nucleotidylexotransferase ; Endothelial cells ; Enzyme Activation - drug effects ; Fibrosis ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Health aspects ; Humans ; Immunohistochemistry ; Kinases ; MAP kinase ; Medical sciences ; Mice ; Mice, Nude ; Miscellaneous ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - metabolism ; Molecular and cellular biology ; Neovascularization, Pathologic - prevention & control ; Nervous system ; Neural stem cells ; Neuroblastoma ; Neuroblastoma - genetics ; Neuroblastoma - metabolism ; Neuroblastoma - pathology ; Neuroblastoma cells ; Neurology ; Neuropeptide Y ; Neuropeptide Y - genetics ; Neuropeptide Y - metabolism ; Neuropeptides ; Pediatrics ; Peptides ; Physiological aspects ; Protein kinase ; Receptors, Neuropeptide Y - antagonists & inhibitors ; Receptors, Neuropeptide Y - genetics ; Receptors, Neuropeptide Y - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA Interference ; siRNA ; Therapeutic targets ; Tumors of the nervous system. Phacomatoses ; Vascularization ; Xenograft Model Antitumor Assays ; Xenografts
É parte de: Oncogene, 2010-10, Vol.29 (41), p.5630-5642
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Descrição: Neuroblastomas are pediatric tumors that develop from sympathetic precursors and express neuronal proteins, such as neuropeptide Y (NPY). NPY is a sympathetic neurotransmitter acting via multiple receptors (Y1-Y5R). Both NPY and Y2Rs are commonly expressed in neuroblastoma cell lines and tissues. The peptide secreted from neuroblastomas stimulates tumor cell proliferation and angiogenesis. As both processes are Y2R-mediated, the aim of this study was to assess Y2R as a potential therapeutic target for neuroblastoma. In vitro, Y2R antagonist (BIIE0246) prevented activation of p44/42 mitogen-activated protein kinase (MAPK) induced by endogenous NPY, which resulted in decreased proliferation and induction of Bim-mediated apoptosis. Similar growth-inhibitory effects were achieved with NPY small interfering RNA (siRNA) and Y2R siRNA. In vivo, Y2R antagonist significantly inhibited growth of SK-N-BE(2) and SK-N-AS xenografts, which was associated with decreased activation of p44/42 MAPK, as well as reduced proliferation (Ki67) and increased apoptosis (TdT-mediated dUTP nick end labeling; TUNEL). The Y2R antagonist also exerted an antiangiogenic effect. In vitro, it reduced the proliferation of endothelial cells induced by neuroblastoma-conditioned media. Consequently, the Y2R antagonist-treated xenografts had decreased vascularization and a high degree of focal fibrosis. In human neuroblastoma tissues, the expression of Y2R was observed in both tumor and endothelial cells, while NPY was predominantly expressed in neuroblastoma cells. In summary, Y2R is a promising new target for neuroblastoma therapy affecting both cancer cells and tumor vasculature.
Editor: Basingstoke: Nature Publishing Group
Idioma: Inglês

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Neuropeptide Y and its Y2 receptor: potential targets in neuroblastoma therapy

LU, C ; EVERHART, L ; ABE, K ; ZUKOWSKA, Z ; TORETSKY, J. A ; KITLINSKA, J ; TILAN, J ; KUO, L ; SUN, C-Cj ; MUNIVENKATAPPA, R. B ; JÖNSSON-RYLANDER, A.-C ; SUN, J ; KUAN-CELARIER, A ; LI, L

Basingstoke: Nature Publishing Group

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