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Changes in gene expression profile in two multidrug resistant cell lines derived from a same drug sensitive cell line

Miguel Angelo Martins Moreira1, Carolina Bagni2, Marcos Barcelos de Pinho1

  • 1Genetics Program, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.

Leukemia Research
|July 6, 2014
PubMed

Insights

Investigating multidrug resistance (MDR) in cancer, this study reveals key gene expression changes in resistant cell lines. ABCB1 overexpression and unmethylated promoters are significant findings in MDR development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genomics

Background:

  • Chemotherapy resistance is a major cause of cancer treatment failure.
  • Cell lines serve as crucial models for investigating the mechanisms underlying drug resistance.
  • Understanding the genetic basis of multidrug resistance (MDR) is vital for developing effective cancer therapies.

Purpose of the Study:

  • To analyze the transcriptional profiles of two multidrug resistant (MDR) cell lines (Lucena 1 and FEPS) derived from the drug-sensitive K562 cell line.
  • To identify differentially expressed genes (DEGs) associated with multidrug resistance.
  • To investigate the role of specific pathways, such as the NOTCH pathway, and genes like ABCB1 in MDR.

Main Methods:

  • Utilized microarray analysis to compare gene expression patterns.
  • Derived and characterized two MDR cell lines (Lucena 1 and FEPS) from a parental drug-sensitive K562 cell line.
  • Quantified gene expression levels and analyzed promoter methylation status of key genes.

Main Results:

  • Identified significant numbers of differentially expressed genes (DEGs) between sensitive and resistant cell lines: 130 (K562 vs. Lucena 1), 1932 (K562 vs. FEPS), and 1211 (Lucena 1 vs. FEPS).
  • The NOTCH pathway was notably affected in the FEPS cell line, with overexpression of NOTCH2 and HEY1.
  • ABCB1 was highly overexpressed in both MDR cell lines, and its promoter was unmethylated in both.

Conclusions:

  • Transcriptional profiling effectively identified genetic alterations associated with multidrug resistance in cancer cell lines.
  • Overexpression of ABCB1, coupled with an unmethylated promoter, is a key characteristic of these MDR cell lines.
  • The NOTCH pathway may play a role in the development of multidrug resistance, warranting further investigation.
Keywords:
ABCB transportersABCB1CancerMDR cell linesMethylationMultidrug resistance

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