Assessing Oxygen Sensitivity of the Multidrug Resistance (MDR) Gene

Abstract

This chapter focuses on assessing oxygen sensitivity of the multidrug resistance (MDR) gene. A major obstacle in the development of effective cancer chemotherapy is tumor development of the multidrug resistance (MDR1) phenotype. Multiple approaches are available to study the function of MDR1/P-gp and how such functions relate to tumor hypoxia. Results of these functional analyses may have broad implications for studying MDR1-expressing tumors and overall chemotherapy resistance. MDR1 expression in patients is most prominent in solid tumors, and MDR1 correlates positively with the propensity of tumors for lymph node spread and metastases. The majority of solid tumors, particularly those with a propensity for P-glycoprotein (P-gp) expression, stain positive for nuclear HIF-1α. This chapter discusses methods for investigating the mechanisms of hypoxia-dependent regulation of MDR1 gene expression in epithelial cells. Analysis of mRNA levels by genechip expression arrays and reverse transcriptase-polymerase chain reaction (RT-PCR), the use of western blotting process, an overview of multicellular dome model, and antisense oligonucleotide treatment of epithelia are discussed.