Basal expression of the multidrug resistance gene 1 (MDR-1) is associated with the TT genotype at the polymorphic site C3435T in mammary and ovarian carcinoma cell lines.
Resistance to established drugs for cancer therapy is in many cases associated with overexpression of the multidrug resistance gene 1 (MDR-1). Regulation of basal expression of MDR-1 and mechanisms of induction as a result of exposure to cytotoxic substances are still not completely understood. Recent reports have suggested an association of the C3435T polymorphism in exon 26 of the MDR-1 gene with MDR-1 expression in duodenal mucosa cells of healthy individuals. We analyzed the C3435T and G2677T genotypes of 38 mammary and ovarian carcinoma cell lines and measured basal MDR-1 expression by real-time reverse transcriptase-polymerase chain reaction. Cell lines were classified as non-expressing or showing weak basal expression that was found to be significantly associated (six/seven versus 13/31 expressing cell lines; P=0.0448, Fisher's exact test) with the TT genotype at position 3435 of the MDR-1 gene.
Sauer
Georg
G
Department of Obstretrics and Gynecology, University of Ulm Medical School, Frauensteige 14, D-89075, Ulm, Germany.
Kafka
Ariane
A
Grundmann
Regina
R
Kreienberg
Rolf
R
Zeillinger
Robert
R
Deissler
Helmut
H
D000230:Adenocarcinoma / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics*; D005838:Genotype; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000737:chemistry; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000235:genetics
D017931:DNA Primers; D001613:beta 2-Microglobulin; D013936:Thymidine