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Related Experiment Videos

Pi-class glutathione S-transferase: regulation and function

C J Henderson1, A W McLaren, G J Moffat

  • 1Ninewells Hospital and Medical School, ICRF Molecular Pharmacology Unit, Dundee, UK. m.rooney@icrf.icnet.uk

Chemico-Biological Interactions
|July 29, 1998
PubMed
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Glutathione S-transferase pi (GST pi) is linked to cancer and drug resistance. Researchers created a mouse model lacking GST pi to study its functions and impact on xenobiotic metabolism.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Glutathione S-transferase pi (GST pi) over-expression is linked to various human cancers and poor prognosis.
  • GST pi plays a role in antineoplastic drug resistance.
  • GST pi gene expression is regulated, with polymorphisms associated with cancer risk.

Purpose of the Study:

  • To investigate the endogenous functions of GST pi.
  • To understand the role of GST pi in carcinogenesis.
  • To create a mouse model for studying GST pi deficiency.

Main Methods:

  • Utilized a multi-drug resistant human mammary carcinoma cell line (MCF7 VCREMS) to study GST P1 transcriptional regulation.
  • Investigated GSTP1 locus polymorphisms (GSTP1a and GSTP1b) and their association with cancer.

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  • Generated a mouse strain deficient in GST pi expression using homologous recombination in embryonic stem cells.
  • Main Results:

    • GST pi over-expression is associated with carcinogenesis and drug resistance.
    • GSTP1b allele linked to increased bladder and testicular cancer; GSTP1a allele decreased in prostate cancer.
    • Created a mouse model completely lacking GST pi expression.

    Conclusions:

    • GST pi is implicated in cancer development, prognosis, and drug resistance.
    • GST pi polymorphisms may influence cancer susceptibility.
    • The developed mouse model offers a novel tool to study the endogenous functions of GST pi and its effects on xenobiotic metabolism.