Inverse expression of mdr 1 and c-myc genes in a rhabdomyosarcoma cell line resistant to actinomycin d

The Journal of Pathology
J PradosA Aránega

Abstract

Cytotoxic agents used in cancer therapy may induce differentiation in tumour cells with no proliferative potential. However, chemotherapy can also induce multidrug resistance, a formidable obstacle to the successful treatment of tumours. Both events were recently shown to occur in a rhabdomyosarcoma cell line (RD-DAC) resistant to actinomycin D, a drug of choice in the treatment of these tumours. To analyse this connection, cell line RD cultures were investigated with progressive concentrations of actinomycin D and it was shown that a minimum dose (1.2 x 10(-6) mM) of the drug was necessary to increase mdr 1 mRNA in RD-DAC. The mechanism of mdr 1 overexpression was an increase in the number of copies of the mdr 1 gene, although the mRNA levels were not correlated with mdr 1 amplification. Drug resistance mediated by mdr 1 overexpression coincided with the development of myogenic differentiation in RD-DAC and with a decrease in c-myc mRNA levels, whereas levels of N-myc mRNA showed no modulation. These findings suggest that factors implicated in cell proliferation and differentiation, such as c-myc, may be responsible for the control of genes related to the development of multidrug resistance in rhabdomyosarcomas. Modulation of ...Continue Reading

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Citations

Jul 1, 1997·The Journal of Laboratory and Clinical Medicine·J A MarchalA Aránega
Sep 2, 1999·Japanese Journal of Cancer Research : Gann·J PradosA Aránega
Mar 5, 2005·Diabetes/metabolism Research and Reviews·Konstantin Bloch, Pnina Vardi
Sep 1, 2008·Expert Review of Clinical Pharmacology·Guillaume DumaisPatrick du Souich
May 15, 2002·Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society·Ivo LeuschnerDieter Harms

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