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

Cancer Lett. 2002 Nov 8;185(1):79-85. doi: 10.1016/s0304-3835(02)00232-x.

Abstract

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.

MeSH terms

  • Adenocarcinoma / genetics*
  • Breast Neoplasms / genetics*
  • DNA Primers / chemistry
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, MDR / genetics*
  • Genotype
  • Humans
  • Ovarian Neoplasms / genetics*
  • Polymorphism, Genetic*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymidine / chemistry
  • Tumor Cells, Cultured
  • beta 2-Microglobulin / genetics

Substances

  • DNA Primers
  • beta 2-Microglobulin
  • Thymidine