Transcriptional and post-transcriptional regulation of glutathione S-transferase P1 expression during butyric acid-induced differentiation of K562 cells.
Over-expression of glutathione S-transferase P1 is related to chemotherapeutic drug resistance as well as to differentiation of human erythroleukemia cells. In opposition to previously described differentiating inducers which enhance the GST-resistance phenotype, time- and concentration-dependent activation of both erythroid and megakaryocytic differentiation pathways by butyric acid progressively diminished GSTP1 mRNA expression. GSTP1 mRNA expression decreased by 25% (p<0.01) and 64% (p<0.01) in 1mM and 2mM butyric acid-differentiated K562 cells, respectively. These results were associated to both a reduction of GATA-1 binding activity to the GSTP1 promoter and to a posttranscriptional destabilization of GSTP1 mRNA in a concentration dependent manner. Indeed, GSTP1 mRNA half-life decreased from 43.8 to 36.2 h and 12.6 h in 1mM- and 2mM-treated cells, respectively.
Schnekenburger
Michael
M
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
Morceau
Franck
F
Henry
Estelle
E
Blasius
Romain
R
Dicato
Mario
M
Trentesaux
Chantal
C
Diederich
Marc
M
D015152:Blotting, Northern; D020148:Butyric Acid / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051549:Glutathione S-Transferase pi / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D020148:Butyric Acid; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi