Abstract
Astrocytic tumors are the most common and the most malignant primary tumors of the central nervous system. We had previously observed that gastrin could significantly modulate both cell proliferation and migration of astrocytoma cells. We have investigated in the present study which genes could be targeted by gastrin in tumor astrocyte migration. Using a subtractive hybridization PCR technique we have cloned genes differentially over-expressed in human astrocytoma U373 cells treated or not with gastrin. We found about 70 genes over-expressed by gastrin. Among the genes overexpressed by gastrin, we paid particular attention to tenascin-C, S100A6 and MLCK genes because their direct involvement in cell migration features. Their gastrin-induced overexpression was quantitatively determined by competitive RT-PCR technique. We also showed by means of a reporter gene system that S100A6 and tenascin-C respective promoters were upregulated after gastrin treatment. These data show that gastrin-mediated effects in glioblastoma cells occur through activation of a number of genes involved in cell migration and suggest that gastrin could be a target in new therapeutic strategies against malignant gliomas.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Amino Acid Sequence
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Biopolymers
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Brain Neoplasms / pathology*
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Cell Cycle Proteins*
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Cell Movement / drug effects
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Cell Movement / genetics
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DNA, Complementary / genetics
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Gastrins / pharmacology*
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic / drug effects*
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Genes, Reporter
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Glioblastoma / pathology*
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Humans
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Molecular Sequence Data
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Myosin-Light-Chain Kinase / biosynthesis
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Myosin-Light-Chain Kinase / genetics
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Myosin-Light-Chain Kinase / physiology
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Neoplasm Invasiveness / genetics
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Neoplasm Proteins / biosynthesis*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology
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Promoter Regions, Genetic / drug effects
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Protein Biosynthesis
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Proteins / genetics
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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RNA, Neoplasm / biosynthesis
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RNA, Neoplasm / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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S100 Calcium Binding Protein A6
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S100 Proteins / biosynthesis
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S100 Proteins / genetics
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S100 Proteins / physiology
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Stress Fibers / metabolism
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Subtraction Technique
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Tenascin / biosynthesis
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Tenascin / genetics
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Tenascin / physiology
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Transfection
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Tumor Cells, Cultured / cytology
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Tumor Cells, Cultured / drug effects
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Wiskott-Aldrich Syndrome Protein Family
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rhoA GTP-Binding Protein / physiology
Substances
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Actins
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Biopolymers
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Cell Cycle Proteins
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DNA, Complementary
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Gastrins
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Neoplasm Proteins
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Proteins
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RNA, Messenger
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RNA, Neoplasm
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S100 Calcium Binding Protein A6
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S100 Proteins
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Tenascin
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WASF1 protein, human
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Wiskott-Aldrich Syndrome Protein Family
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S100A6 protein, human
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gastrin 17
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Myosin-Light-Chain Kinase
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rhoA GTP-Binding Protein