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Overexpression of human phosphoglycerate kinase 1 (PGK1) induces a multidrug resistance phenotype

Z Duan1, D E Lamendola, R Z Yusuf

  • 1Department of Hematology/Oncology, Massachusetts General Hospital, Boston 02114, USA.

Anticancer Research
|August 15, 2002
PubMed
Abstract

Insights

Phosphoglycerate kinase 1 (PGK1) can cause multidrug resistance in cancer cells. This study identified PGK1 as a key factor in paclitaxel resistance, independent of MDR-1 mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Multidrug resistance (MDR) is a major obstacle in effective cancer chemotherapy.
  • Identifying genetic factors contributing to MDR is crucial for developing new treatment strategies.

Purpose of the Study:

  • To identify specific genetic alterations responsible for paclitaxel resistance.
  • To investigate the role of phosphoglycerate kinase 1 (PGK1) in conferring multidrug resistance.

Main Methods:

  • A functional cloning strategy using a cDNA library from paclitaxel-resistant ovarian cancer cells (SW626TR).
  • Transfection of the library into paclitaxel-sensitive osteosarcoma cells (U-20S) to isolate resistant clones.
  • DNA sequencing, enzymatic assays, and gene expression analysis (Northern, Western blots) to characterize the identified gene and its function.

Main Results:

  • Clone C16 was identified as human phosphoglycerate kinase 1 (PGK1).
  • Retransfection of PGK1 into U-20S cells induced a 30-fold increase in paclitaxel resistance and cross-resistance to other drugs (vincristine, adriamycin, mitoxantrone).
  • Increased PGK1 activity was observed, but MDR-1 expression and verapamil sensitivity remained unchanged, indicating an MDR-1 independent mechanism.

Conclusions:

  • Phosphoglycerate kinase 1 (PGK1) can induce a multidrug resistant phenotype.
  • The mechanism of PGK1-mediated multidrug resistance is independent of the MDR-1 gene.

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