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.
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Acknowledgements
We gratefully thank Dr X Tu (T Jefferson University, Philadelphia, PA, USA) for providing p2A9-CAT vectors. We are also grateful to Dr B Binétruy (University of Nice Sophia-Antipolis, Nice, France) for tenascin-C CAT constructs and Dr R Chiquet (Friedrich Miescher Institute, Basel, Switzerland) for tenascin-C luciferase construct. The present work has been carried out on the basis of grants awarded by the Centre National de Recherche Scientifique (CNRS, France), by the Ministère de l'Enseignement Supérieur et de la Recherche and by the Fonds National de la Recherche Scientifique (FNRS, Belgium). C Decaestecker and R Kiss are a Research Associate and a Senior Research Associate with the FNRS. I Camby is the holder of a grant from the Rose & Jean Hoguet Foundation.
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Kucharczak, J., Pannequin, J., Camby, I. et al. Gastrin induces over-expression of genes involved in human U373 glioblastoma cell migration. Oncogene 20, 7021–7028 (2001). https://doi.org/10.1038/sj.onc.1204882
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DOI: https://doi.org/10.1038/sj.onc.1204882
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