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INVERSE EXPRESSION OF mdr 1 AND c‐ myc GENES IN A RHABDOMYOSARCOMA CELL LINE RESISTANT TO ACTINOMYCIN D
Author(s) -
PRADOS JOSE,
MELGUIZO CONSOLACIÓN,
FERNÁNDEZ ALBERTO,
ARÁNEGA AMELIA E.,
ALVAREZ LUIS,
ARÁNEGA ANTONIA
Publication year - 1996
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199609)180:1<85::aid-path626>3.0.co;2-7
Subject(s) - rhabdomyosarcoma , cell culture , multiple drug resistance , cancer research , biology , gene , drug resistance , messenger rna , gene expression , microbiology and biotechnology , sarcoma , medicine , genetics , pathology
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 (1·2×10 −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 these factors may determine the sensitivity of rhabdomyosarcoma cells to drugs and may play an important role in triggering the differentiation programme found in these resistant rhabdomyosarcoma cells.