Relationship between expression of mutant type glutathione S-transferase theta-1 gene and reactivity of rapamycin in myelodysplastic syndrome.
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.
Division of Hematology, Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan. ymaeda@med.kindai.ac.jp
Yasuhiro
Y
Maeda
Terufumi
T
Yamaguchi
Atsushi
A
Sasakawa
Miyako
M
Tanaka
Yasuyoshi
Y
Morita
Shuhei
S
Kawata
Katsuya
K
Watanabe
Chikara
C
Hirase
Shunsuke
S
Takai
Junichi
J
Miyatake
Yoichi
Y
Tatsumi
Akihisa
A
Kanamaru
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases
D000903:Antibiotics, Antineoplastic; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus