Expression of MDR1/p-glycoprotein and multidrug resistance-associated protein in childhood solid tumours

Abstract

We evaluated the expression of MDR1/p-glycoprotein in paediatric tumours using reverse transcriptase polymerase chain reaction (RT-PCR), RNA dot blot analysis, and immunohistochemistry on formalin fixed paraffin-embedded material with JSB-1 and C-219 monoclonal antibodies, and compared these three techniques. The expression of multidrug resistance-associated protein (MRP) gene was examined by RT-PCR assay. We studied MDR1/p-glycoprotein and MRP expression in 13 samples from 10 neuroblastoma patients, 11 samples from 10 nephroblastoma patients, 2 rhabdomyosarcomas, 1 adrenocortical carcinoma and 10 benign tumours or tumour-like lesions. Eleven of 13 neuroblastomas, 7 of 11 nephroblastomas, 2 rhabdomyosarcomas, 1 adrenocortical carcinoma, and 7 of 10 benign tumours or tumour-like lesions showed MDR1 PCR products. By RNA dot blot analysis, MDR1 transcripts were detectable in 11 of 34 specimens. Immunohistochemically, we detected positive reaction products for JSB-1 in 26 of 36 samples. There was a significant correlation between the immunoreactivity for JSB-1 and the expression of MDR1 mRNA expression by RT-PCR (P = 0.0001). However, the presence of p-glycoprotein immunostaining does not correlate with the MDR1 expression shown by RT-PCR in every case. As for MRP mRNA expression, 9 of 13 neuroblastomas and 10 of 11 nephroblastomas revealed PCR products.

Effects on P-Glycoprotein Expression after Blood-Brain Barrier Disruption Using Focused Ultrasound and Microbubbles

“…The sample size was relatively small for the individual experimental groups, and more experiments could yield improved estimates of the length of time that Pgp is suppressed and reveal additional correlations between Pgp suppression and other factors. Use of different techniques to evaluate Pgp expression, such as reverse transcriptase polymerase chain reaction (RT-PCR) or RNA dot blot analysis [52], should be performed to confirm these findings.…”

Modulation of Myogenic Differentiation in a Human Rhabdomyosarcoma Cell Line by a New Derivative of 5‐Fluorouracil (QF‐3602)

“…6) The frequent failure of cytotoxic therapy in these tumors may be related to the development of drug resistance. 7) Significant increases in mdr 1/P-glycoprotein expression have been detected in RMS after chemotherapy in vivo 8) and in vitro. 9) However, the cytotoxic treatment of RMS has demonstrated that these tumor cells can be induced to re-enter the differentiation process, 10,11) supporting the hypothesis that RMS arises from skeletal muscle cells which are arrested along the normal myogenic pathway to maturation.…”

A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier

“…It was first observed and described in drug-resistant cancer cells that highly expressed it. In breast cancer cells, P-gp prevents effective chemotherapeutic treatment by blocking chemotherapeutic drug uptake (17)(18)(19). Later studies showed that P-gp is also highly expressed on capillaries of the liver, sex organs, and the brain and is involved in expulsion of xenobiotics from the CNS (20)(21)(22)(23).…”