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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Biomarcadores > DA - CIMA - Oncología - Biomarcadores - Artículos de Revista >

Gene expression profiling identifies IL-13 receptor alpha 2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin
Authors: Gonzalez-Moreno, O. (Óscar)
Calvo, A. (Alfonso)
Joshi, B.H. (Bharat H.)
Abasolo, I. (Ibane)
Leland, P. (Pamela)
Wang, Z. (Zhou)
Montuenga, L.M. (Luis M.)
Puri, R.K. (Raj K.)
Green, J.E. (Jeffrey E.)
Keywords: cDNA microarrays
Prostate cancer
Adrenomedullin
IL-13Ralpha2
Gene expression profiling
Issue Date: 2005
Publisher: Wiley Blackwell
Publisher version: http://onlinelibrary.wiley.com/doi/10.1002/ijc.20789/abstract
ISSN: 1097-0215
Citation: Gonzalez-Moreno O, Calvo A, Joshi BH, Abasolo I, Leland P, Wang Z, et al. Gene expression profiling identifies IL-13 receptor alpha 2 chain as a therapeutic target in prostate tumor cells overexpressing adrenomedullin. Int J Cancer 2005 May 10;114(6):870-878.
Abstract
Human adrenomedullin (AM) is a 52 amino acid peptide, which shares homology with the calcitonin gene-related peptide. Overexpression of AM in the prostate carcinoma cell line PC-3 results in growth inhibition with a 20% (for human AM) and 35% (for rat AM) increase in doubling time compared to parental or mock-transfected cells. We demonstrate by gene expression profiling that AM overexpression results in the dysregulation of approximately 100 genes. Examples of such genes include many involved in the formation of the cytoskeleton, cell adhesion and the extracellular matrix, as well as regulators of the cell cycle and apoptosis, cytokines and transcription factors. Several genes related to cell growth arrest, such as GADD45, IGF-BP6 and RUNX-3, are upregulated by AM. Interestingly, interleukin-13 receptor alpha 2 (IL-13R alpha 2) transcripts were significantly increased in clones overexpressing AM, which was confirmed by semiquantitative RT-PCR analysis. In addition, PC-3 cells treated with AM showed an overexpression of IL-13R alpha 2, which was abolished when cells were preincubated with an anti-AM blocking antibody. When PC-3 cells overexpressing AM and the IL-13R alpha 2 were treated with the highly specific IL13-PE38 cytotoxin, which binds to this receptor, a concentration-dependent inhibition of protein synthesis was observed. The IC(50) (concentration of cytotoxin inhibiting protein synthesis by 50%) ranged from 1 to 4 ng/ml. This cytotoxicity was specific as it was neutralized by the excess of IL-13 and confirmed by clonogenic assays. This study describes a novel AM-induced mechanism of tumor sensitization through the upregulation of functional IL-13R alpha 2 chain, an ideal target for the highly specific recombinant chimeric cytotoxin IL13-PE38.
Permanent link: http://hdl.handle.net/10171/20176
Appears in Collections:DA - CIMA - Oncología - Nuevas dianas terapéuticas - Artículos de revista
DA - Ciencias - HAP - Artículos de revista
DA - CIMA - Oncología - Biomarcadores - Artículos de Revista

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