Related Experiment Videos
The multidrug-resistance gene MDR1 is expressed in human glial tumors
I Becker1, K F Becker, R Meyermann
1Institut für Hirnforschung Universität Tübingen, Federal Republic of Germany.
Abstract:
The most consistantly reported alteration of multidrug-resistant carcinoma cells is the overexpression of a membrane glycoprotein, termed P-glycoprotein. In this study we examined whether the strong intrinsic chemotherapy resistance of glial tumors might be related to the expression of the MDR1 gene which codes for P-glycoprotein. Fourteen glial tumors were examined immunohistochemically using the monoclonal antibody C219. In addition, RNA samples of 11 of these tumors were analysed using a sensitive Northern blot assay. P-glycoprotein is expressed in all 14 glial tumors; the number of stained tumor cells, however, varied considerably ranging from 0.3% to 15%. There was no correlation between the number of MDR1-positive cells and the histological malignancy. Varying amounts of MDR1 mRNA were detectable in 7 from 11 examined tumors. The results of our study show that the MDR1 gene is expressed in human glial tumors and suggest that the multidrug transporter may contribute to the clinical non-responsiveness of these tumors to chemotherapy.
Insights
Multidrug resistance in glial tumors may stem from P-glycoprotein (MDR1 gene product) overexpression. This study found P-glycoprotein expression in all examined tumors, suggesting its role in chemotherapy resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy.
- P-glycoprotein, encoded by the MDR1 gene, is a key mediator of MDR in various carcinoma cells.
- Glial tumors exhibit intrinsic resistance to chemotherapy, but the underlying mechanisms are not fully understood.
Purpose of the Study:
- To investigate the expression of the MDR1 gene and its product, P-glycoprotein, in human glial tumors.
- To determine if P-glycoprotein expression correlates with the histological malignancy of glial tumors.
- To assess the potential contribution of P-glycoprotein to the chemotherapy resistance observed in glial tumors.
Main Methods:
- Immunohistochemical analysis of 14 glial tumors using the monoclonal antibody C219 to detect P-glycoprotein.
- Northern blot assay to analyze MDR1 mRNA expression in RNA samples from 11 of the tumors.
- Correlation analysis between P-glycoprotein expression levels, MDR1 mRNA levels, and histological malignancy grade.
Main Results:
- P-glycoprotein was detected in all 14 glial tumors, with varying percentages of positive cells (0.3%–15%).
- No significant correlation was found between the number of MDR1-positive cells and the histological malignancy grade.
- MDR1 mRNA was detectable in 7 out of 11 examined tumors, indicating active gene expression.
Conclusions:
- The MDR1 gene is expressed in human glial tumors.
- P-glycoprotein, a multidrug transporter, is present in glial tumors.
- These findings suggest that P-glycoprotein may contribute to the intrinsic chemotherapy resistance of glial tumors, impacting clinical treatment outcomes.