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Doxorubicin-Induced Alterations of c-myc and c-jun Gene Expression in Rat Glioblastoma Cells: Role of c-jun in Drug Resistance and Cell Death

Abstract : We studied the effect of doxorubicin on the expression of c-myc and c-jun in the rat glioblastoma cell line C6 and its doxorubicin-resistant variant C6 0.5, at equitoxic exposures. For quantitation, the mRNA levels of these oncogenes were related to those of two domestic genes, beta-actin and glyceraldehyde phosphate dehydrogenase. After a transient overexpression of the genes during the first hour of incubation, there was a selective, dose-dependent down-regulation of both genes by doxorubicin in the sensitive cells. In the resistant cell line, c-myc expression was also decreased in response to doxorubicin incubation, but the expression of c-jun remained unchanged over the whole range of concentrations. In contrast, vincristine had no effect on the amounts of c-myc and c-jun mRNAs in either line. The effect of doxorubicin on the mRNA levels of c-jun was also observed on the JUN proteins by immunoblotting, but the MYC protein levels remained unchanged upon doxorubicin treatment. There was a significant correlation between the levels of c-myc and c-jun gene expression and the degree of growth inhibition induced by doxorubicin. In addition, doxorubicin induced a fragmentation of DNA in sensitive cells, but not in resistant cells, thus revealing a resistance to apoptosis in this line. Doxorubicin-induced cell death did not appear to be mediated by p53 in either cell line.
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https://www.hal.inserm.fr/inserm-02438237
Contributor : Philippe Pourquier <>
Submitted on : Tuesday, January 14, 2020 - 10:34:17 AM
Last modification on : Tuesday, March 17, 2020 - 2:31:56 AM

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Philippe Pourquier, Danièle Montaudon, Sylvie Huet, Annick Larrue, Audrey Clary, et al.. Doxorubicin-Induced Alterations of c-myc and c-jun Gene Expression in Rat Glioblastoma Cells: Role of c-jun in Drug Resistance and Cell Death. Biochemical Pharmacology, Elsevier, 1998, 55 (12), pp.1963-1971. ⟨10.1016/s0006-2952(98)00006-9⟩. ⟨inserm-02438237⟩

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