Abstract
Gastrin-releasing peptide (GRP) has been proposed as a major growth factor in brain tumors, and GRP receptor (GRPR) antagonists show antiproliferative effects in experimental gliomas. However, the underlying molecular events downstream of GRPR activation remain poorly understood. In the present study, we examined the role of the GRPR in regulating proliferation of glioma cells in vitro and its possible interaction with the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Expression of GRPR mRNA and protein in C6, U-87MG, and U-373MG glioma cells was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Proliferation of C6 and U-87MG, but not U-373MG cells was significantly inhibited by the GRPR antagonist RC-3095, whereas the GRPR agonist bombesin (BB) significantly enhanced proliferation of C6 cells. The BB-induced stimulatory effect on cell proliferation was prevented by either RC-3095 or the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Our results provide the first evidence that the GRPR regulates proliferation of C6 glioma cells and suggest that PI3K is required for GRPR-mediated stimulation of glioma growth.
Keywords: Bombesin-like peptides, gastrin-releasing peptide receptor, RC-3095, phosphoinositide 3-kinase, glioma, brain tumor
Current Neurovascular Research
Title: Gastrin-Releasing Peptide Receptors Regulate Proliferation of C6 Glioma Cells through a Phosphatidylinositol 3-Kinase-Dependent Mechanism
Volume: 5 Issue: 2
Author(s): Debora Gazzana Flores, Caroline Brunetto de Farias, Juliano Leites, Marianne Schrader de Oliveira, Rodrigo Cruz Lima, Alessandra Sayuri Kikuchi Tamajusuku, Luciane Pons Di Leone, Luise Meurer, Algemir Lunardi Brunetto, Gilberto Schwartsmann, Guido Lenz and Rafael Roesler
Affiliation:
Keywords: Bombesin-like peptides, gastrin-releasing peptide receptor, RC-3095, phosphoinositide 3-kinase, glioma, brain tumor
Abstract: Gastrin-releasing peptide (GRP) has been proposed as a major growth factor in brain tumors, and GRP receptor (GRPR) antagonists show antiproliferative effects in experimental gliomas. However, the underlying molecular events downstream of GRPR activation remain poorly understood. In the present study, we examined the role of the GRPR in regulating proliferation of glioma cells in vitro and its possible interaction with the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Expression of GRPR mRNA and protein in C6, U-87MG, and U-373MG glioma cells was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Proliferation of C6 and U-87MG, but not U-373MG cells was significantly inhibited by the GRPR antagonist RC-3095, whereas the GRPR agonist bombesin (BB) significantly enhanced proliferation of C6 cells. The BB-induced stimulatory effect on cell proliferation was prevented by either RC-3095 or the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Our results provide the first evidence that the GRPR regulates proliferation of C6 glioma cells and suggest that PI3K is required for GRPR-mediated stimulation of glioma growth.
Export Options
About this article
Cite this article as:
Flores Gazzana Debora, de Farias Brunetto Caroline, Leites Juliano, de Oliveira Schrader Marianne, Lima Cruz Rodrigo, Kikuchi Tamajusuku Sayuri Alessandra, Di Leone Pons Luciane, Meurer Luise, Brunetto Lunardi Algemir, Schwartsmann Gilberto, Lenz Guido and Roesler Rafael, Gastrin-Releasing Peptide Receptors Regulate Proliferation of C6 Glioma Cells through a Phosphatidylinositol 3-Kinase-Dependent Mechanism, Current Neurovascular Research 2008; 5 (2) . https://dx.doi.org/10.2174/156720208784310240
DOI https://dx.doi.org/10.2174/156720208784310240 |
Print ISSN 1567-2026 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5739 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Farnesyltransferase Inhibitors: A Comprehensive Review Based on Quantitative Structural Analysis
Current Medicinal Chemistry Dietary Polyphenols for Prostate Cancer Therapy
Current Bioactive Compounds Eicosanoids Derived From Arachidonic Acid and Their Family Prostaglandins and Cyclooxygenase in Psychiatric Disorders
Current Neuropharmacology Comparing the Interaction of Cyclophosphamide Monohydrate to Human Serum Albumin as Opposed to Holo-Transferrin by Spectroscopic and Molecular Modeling Methods: Evidence for Allocating the Binding Site
Protein & Peptide Letters Histone Variants and Composition in the Developing Brain: Should MeCP2 Care?
Current Topics in Medicinal Chemistry Systematic Analysis of RNAi Reports Identifies Dismal Commonality at Gene-Level and Reveals an Unprecedented Enrichment in Pooled shRNA Screens
Combinatorial Chemistry & High Throughput Screening Chidamide Inhibits Cell Proliferation via the PI3K/AKT Pathway in K562 Cells Based on Network Pharmacology and Experimental Validation
Current Pharmaceutical Design Environmental Risk Assessment of Replication Competent Viral Vectors Applied in Clinical Trials: Potential Effects of Inserted Sequences
Current Gene Therapy Inhibition of Glycolysis and Glutaminolysis: An Emerging Drug Discovery Approach to Combat Cancer
Current Topics in Medicinal Chemistry Analysis of miRNAs Targeting 3’UTR of H2AFX Gene: a General <i>in Silico</i> Approach
MicroRNA Iron Oxide Nanoparticles Synthesized Via Green Tea Extract for Doxorubicin Delivery
Current Nanoscience Seizures and Anticonvulsants in Brain Tumours: Frequency, Mechanisms and Anti-Epileptic Management
Current Pharmaceutical Design Recent Advances in Optical Cancer Imaging of EGF Receptors
Current Medicinal Chemistry Brain Tumour Stem Cells: Implications for Cancer Therapy and Regenerative Medicine
Current Stem Cell Research & Therapy The Hippocampal Autophagic Machinery is Depressed in the Absence of the Circadian Clock Protein PER1 that may Lead to Vulnerability During Cerebral Ischemia
Current Neurovascular Research Virtual Screening of Acetylcholinesterase Inhibitors Based on Machine Learning Combined with Molecule Docking Methods
Current Bioinformatics Ginsenoside Rh2 Inhibits Migration of Lung Cancer Cells under Hypoxia via mir-491
Anti-Cancer Agents in Medicinal Chemistry Transmembrane Protein 166 and its Significance
Protein & Peptide Letters Methylenetetrahydrofolate Reductase (MTHFR): A Novel Target for Cancer Therapy
Current Pharmaceutical Design Targeting the Voltage-Dependent K+ Channels Kv1.3 and Kv1.5 as Tumor Biomarkers for Cancer Detection and Prevention
Current Medicinal Chemistry