Relationship between expression of mutant type glutathione S-transferase theta-1 gene and reactivity of rapamycin in myelodysplastic syndrome

Hematology. 2009 Oct;14(5):266-70. doi: 10.1179/102453309X439827.

Abstract

We previously reported mRNA expression of glutathione S-transferases theta (GSTT)-1, wild type (623 bp) and mutant (500 bp), in patients with myelodysplastic syndrome (MDS). The deletion of 123 bp creates a sequence that is homologous to the mammalian target of rapamycin (mTOR). To analyze the function of mutant GSTT-1 gene, stable transformants for the mutant and wild-type GSTT-1 gene, respectively, were established. In this study, the expression of the wild and mutant type of the GSTT-1 gene of those stable transformants in cell lines and in bone marrow cells from MDS patients by reverse-transcription polymerase chain reaction (RT-PCR) was observed in the presence or absence of rapamycin. Significant growth inhibition by rapamycin was observed among stable transformants for the mutant GSTT-1 gene, but not wild type GSTT-1 gene, and was indicative of typical apoptosis.

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Enzymologic / genetics
  • Glutathione Transferase / biosynthesis*
  • Glutathione Transferase / genetics
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Mutation*
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / enzymology*
  • Myelodysplastic Syndromes / genetics
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Sirolimus / pharmacology*
  • TOR Serine-Threonine Kinases

Substances

  • Antibiotics, Antineoplastic
  • glutathione S-transferase T1
  • Glutathione Transferase
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus