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Co-amplification and over-expression of two mdr genes in a multidrug-resistant human colon carcinoma cell line
1Department of Biochemistry, Chang Gung Medical College, Taoyuan, Taiwan, Republic of China.
Abstract:
The human P-glycoprotein gene family contains the mdr1 and the mdr3 gene. The mdr1 P-glycoprotein is over-expressed in multidrug resistant (MDR) tumor cells and is believed to play a role in the elimination of certain cytotoxic drugs used in the chemotherapy of cancer. The mdr3 gene has not been found to be amplified or over-expressed in MDR cells. In this study, gene-specific mdr gene probes were developed for the detection of the gene and the total mRNA level. Southern and Northern hybridization analyses showed that the mdr genes and the mRNA levels were increased 30--40-fold in a MDR human colon cancer cell line. In addition, this MDR cell line had an altered growth rate and morphology and detectable double minute chromosomes.
Insights
Multidrug resistant (MDR) cancer cells show a 30-40 fold increase in mdr genes and mRNA. This study investigated mdr gene expression in MDR human colon cancer cells, revealing significant overexpression.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- The human P-glycoprotein gene family includes mdr1 and mdr3.
- MDR1 P-glycoprotein is overexpressed in multidrug-resistant (MDR) tumor cells, potentially mediating drug efflux.
- MDR3 gene amplification or overexpression in MDR cells has not been previously observed.
Purpose of the Study:
- To develop gene-specific probes for detecting mdr genes and mRNA levels.
- To investigate the expression of mdr genes in a multidrug-resistant human colon cancer cell line.
- To correlate mdr gene expression with cellular changes in MDR cancer cells.
Main Methods:
- Development of gene-specific mdr probes.
- Southern and Northern hybridization analyses.
- Characterization of MDR cell line morphology, growth rate, and chromosomal abnormalities.
Main Results:
- Southern and Northern hybridization revealed a 30-40 fold increase in mdr genes and mRNA levels in the MDR colon cancer cell line.
- The MDR cell line exhibited altered growth rate and morphology.
- Detectable double minute chromosomes were observed in the MDR cell line.
Conclusions:
- The study demonstrates significant overexpression of mdr genes and mRNA in a multidrug-resistant human colon cancer cell line.
- These findings suggest a role for mdr gene amplification in the development of multidrug resistance in this cancer model.
- The observed cellular alterations and chromosomal abnormalities in the MDR cell line warrant further investigation.
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