B. Vanhille et al., ASSESSMENT OF DRUG-INDUCED DYSREGULATIONS AMONG 7 RESISTANCE-ASSOCIATED GENES IN HUMAN TUMOR-CELL LINES, Anticancer research, 16(6B), 1996, pp. 3531-3536
Drug-resistance in cell lines and in malignant human tumours is associ
ated with dysregulation of several genes, including mdr1, MRP1, GST-pi
, bcl-2, DNA topoisomerase II alpha and beta, and thymidine kinase I.
mRNA expression was evaluated by quantitative RT-PCR coupled with HPLC
in three human tumour cell lines and drug-resistant (DR)-sublines. DR
sublines from RPMI-8226 and KB cells specifically overexpressed the m
dr1 gene without major changes observed in other putative DR-associate
d genes. In contrast, the DR-H69 cells exhibited a 34-fold overexpress
ion of the MRP gene accompanied by significant down-regulation of both
DNA topoisomerase II alpha and bcl-2 mRNA gene expression, by factors
of 43 and 13, respectively. These results demonstrate the concomitant
down-regulation of topoisomerase II alpha and bcl-2 genes in response
to DR. Furthermore, differential patterns of gene dysregulations appe
ar to vary depending upon both the drug used to select resistance and
cellular origin.