Co-amplification and over-expression of two mdr genes in a multidrug-resistant human colon carcinoma cell line

C C Chao1, C M Ma, S Lin-Chao

  • 1Department of Biochemistry, Chang Gung Medical College, Taoyuan, Taiwan, Republic of China.

FEBS Letters
|October 21, 1991
PubMed

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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