Functional analysis of the effect of forced activation of STAT3 on M1 mouse leukemia cells.
M1 mouse myeloid leukemia cells exhibit growth arrest and differentiation to monocytes/macrophages in response to leukemia inhibitory factor (LIF) stimulation. Although recent studies have demonstrated that STAT3 plays a central role in this process, it is unknown whether STAT3 activation alone is sufficient. To address this issue, we have established M1/STAT3ER cells, where STAT3 is selectively activated by 4-hydroxytamoxifen (4HT). 4HT stimulation did not have any effect on growth and morphology of M1/ STAT3ER cells, and did not induce the down-regulation of mRNA of c-myc and c-myb, which is necessary for M1 cell differentiation. On the other hand, mRNA of jun-B, IRF1 and p19 was increased by 4HT. DNA precipitation assay indicated that both stimulation of LIF and 4HT similarly activated STAT3ER. Introduction of a constitutive active MAP kinase kinase (MEK1) into M1/STAT3ER cells did not induce differentiation either. Together, our present data suggest that signaling other than the activation of STAT3 and MEK1 may be necessary for M1 cell-growth arrest and differentiation, while a set of early genes of LIF are induced by only STAT3 activation.
Yoshida
Tsunehiko
T
Department of Ophthalmology, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
Iwamoto
Takashi
T
Adachi
Koichi
K
Yokota
Takashi
T
Miyake
Yozo
Y
Hamaguchi
Michinari
M
D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050764:Cyclin-Dependent Kinase Inhibitor p19; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D004789:Enzyme Activation; D004965:Estrogen Antagonists / Q000494:pharmacology; D015151:Immunoblotting; D050856:Interferon Regulatory Factor-1; D015850:Interleukin-6 / Q000378:metabolism; D007938:Leukemia / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D051379:Mice; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*
C493975:Cdkn2d protein, mouse; D018797:Cell Cycle Proteins; D050764:Cyclin-Dependent Kinase Inhibitor p19; D004268:DNA-Binding Proteins; D004965:Estrogen Antagonists; D050856:Interferon Regulatory Factor-1; D015850:Interleukin-6; C494258:Irf1 protein, mouse; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D016759:Oncogene Protein p65(gag-jun); D010750:Phosphoproteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D013629:Tamoxifen; C016601:afimoxifene; D004247:DNA; D048369:MAP Kinase Kinase 1