STAT3-mediated differentiation and survival of myeloid cells in response to granulocyte colony-stimulating factor: role for the cyclin-dependent kinase inhibitor p27Kip1

Koning, John P. de; Soede-Bobok, Amrita A.; Ward, Alister C.; Schelen, Anita M.; Antonissen, Claudia; Leeuwen, Daphne van; Löwenberg, Bob; Touw, Ivo P.

doi:10.1038/sj.onc.1203627

Cited by 120 publications

(127 citation statements)

References 53 publications

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“…The mouse myeloid cell line 32D/WT1, ectopically expressing human granulocyte colony stimulating factor (G-CSF) (de Koning et al, 1998), was maintained in the presence of 10 ng/ ml of murine interleukin-3 (IL3) (BD Biosciences, San Jose, CA, USA) in RPMI 1640 medium supplemented with 10% fetal calf serum, 1% antibiotics (penicillin/streptomycin), adjusting the cell density to 2 Â 10 5 cells/ml daily. To induce granulocyte differentiation, cells were washed in RPMI medium, and IL-3 was replaced with 10 ng/ml human G-CSF (Amgen, Thousand Oaks, CA, USA).…”

Section: Cell Culturementioning

confidence: 99%

Myeloid maturation block by AML1-MTG16 is associated with Csf1r epigenetic downregulation

et al. 2005

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De novo epigenetic changes at histone and DNA level that affect gene transcription in cancer may be less random than we originally thought. Leukemia fusion proteins associated with specific chromosome translocations could mechanistically determine the epigenetic fate of specific target genes critical for normal hematopoiesis. This seems to be the case with AML1-MTG16, a fusion protein resulting from the t(16;21) translocation, a hallmark of therapy-related leukemia and myelodysplastic syndrome. Here we show that AML1-MTG16 blocks both myeloid differentiation and proliferation in the 32D/WT1-mouse myeloid cell line. These biological effects can be traced to the AML1 and MTG16 moieties of the fusion protein, respectively. Further, we show that AML1-MTG16 can induce epigenetic repressive changes at the histone and DNA level of the AML1 target gene Csf1r (c-fms), encoding the macrophage colony stimulating factor receptor. We observed that, concomitant with Csf1r downregulation, 32D/WT1 cells lost the ability to undergo myeloid differentiation in response to the granulocyte macrophage colony-stimulating factor (GM-CSF). Thus, there seems to be an association between AML1-MTG16-induced myeloid maturation block and epigenetic changes of a myeloid master gene.

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Section: Cell Culturementioning

confidence: 99%

Myeloid maturation block by AML1-MTG16 is associated with Csf1r epigenetic downregulation

et al. 2005

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“…Stat3 activation has been linked to both growth arrest and to aberrant cell growth, to apoptosis and antiapoptosis, and to cell migration (Akira, 2000). During hematopoiesis, Stat3 is required for myeloid differentiation (Steinman and Iro, 1999;McLemore et al, 2001) and facilitates differentiation-coupled growth arrest by inducing the transcription of the cell cycle inhibitor p27 (de Koning et al, 2000). In contrast, several leukemogenic oncogenes have been found to promote constitutive Stat3 activation in cell line models and in leukemic blasts.…”

Section: Introductionmentioning

confidence: 99%

Activation of Stat3 by cell confluence reveals negative regulation of Stat3 by cdk2

Steinman

Wentzel

et al. 2003

Oncogene

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The signal transducing protein Stat3 activates gene transcription in cells in response to multiple cytokines. Constitutive activation of Stat3 has been observed in solid tumors including head and neck squamous cell carcinoma. Stat3 activation in cancer has been associated with autocrine stimulatory loops and is believed to convey a growth advantage to cells. We now demonstrate ligandindependent activation of Stat3 by high cell density in multiple cancer cell lines. Activation of Stat3 is associated with antiproliferative rather than proliferative conditions. Interference with cdk2 activity upregulates Stat3 phosphorylation and Stat3-directed DNA-binding activity. Our data supports a model in which Stat3 activity is partially suppressed by cdk2 in growing cells and derepressed upon cell confluence.

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“…Similarly, STAT5 and Sp1 were shown to regulate transcription of the cyclin D2 gene in response to IL-2 (Martino et al, 2001), and STAT3 and Sp1 were shown to activate transcription of the C/EBPd gene in hepatocytes in response to IL-6 (Cantwell et al, 1998). Stat3 is known to be activated in response to G-CSF and has been shown to play an essential role in G-CSFdependent granulocytic differentiation both in vitro (de Koning et al, 2000) and in vivo (McLemore et al, 2001). Our evidence suggests that G-CSF-dependent activation of Stat3 results in binding of activated Stat3 to the Jak3 promoter to activate Jak3 transcription in concert with Sp1.…”

Section: Discussionmentioning

confidence: 63%

“…This constitutively active mutant of Stat3 (Stat3-C) has been shown to dimerize spontaneously in the absence of tyrosine phosphorylation, bind to DNA, and activate transcription of target molecules (Bromberg et al, 1999). Stat3 was an attractive candidate to play a role in Jak3 transcription during myeloid differentiation because it is known to be phosphorylated in response to G-CSF (Ihle, 1996;Chakraborty and Tweardy, 1998;Rane and Reddy, 2000), and previous studies have suggested an essential role for Stat3 in granulocytic differentiation (de Koning et al, 2000;McLemore et al, 2001). Figure 4a shows the effect of Stat3 on Jak3 promoter activity in G-CSF-stimulated 32Dcl3 cells.…”

Section: Resultsmentioning

confidence: 99%

Granulocyte colony-stimulating factor-induced upregulation of Jak3 transcription during granulocytic differentiation is mediated by the cooperative action of Sp1 and Stat3

et al. 2006

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We previously demonstrated that Jak3 is a primary response gene for G-CSF and ectopic overexpression of Jak3 can accelerate granulocytic differentiation of normal mouse bone marrow cells induced by G-CSF and GM-CSF. To gain insight into the regulation of G-CSFinduced transcription of Jak3, we constructed deletion and linker scanning mutants of the Jak3 promoter sequences and performed luciferase reporter assays in the murine myeloid cell line 32Dcl3, with and without G-CSF stimulation. These experiments showed that mutation of a À67 to À85 element, which contained a putative Sp1 binding site, or mutation of a À44 to À53 GAS element resulted in a marked reduction of Jak3 promoter activity. Electrophoretic mobility shift assays revealed that Sp1 and Stat3 present in nuclear lysates of 32Dcl3 cells stimulated with G-CSF can bind to the À67 to À85 element and À44 to À53 GAS element, respectively. In addition, cotransfection of a constitutively active mutant of Stat3 along with a Jak3 promoter/luciferase reporter resulted in enhanced Jak3 promoter activity. Together, these results demonstrate that activation of Jak3 transcription during G-CSF-induced granulocytic differentiation is mediated by the combined action of Sp1 and Stat3, a mechanism also shown to be important in IL-6-induced monocytic differentiation.

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STAT3-mediated differentiation and survival of myeloid cells in response to granulocyte colony-stimulating factor: role for the cyclin-dependent kinase inhibitor p27Kip1

Cited by 120 publications

References 53 publications

Myeloid maturation block by AML1-MTG16 is associated with Csf1r epigenetic downregulation

Myeloid maturation block by AML1-MTG16 is associated with Csf1r epigenetic downregulation

Activation of Stat3 by cell confluence reveals negative regulation of Stat3 by cdk2

Granulocyte colony-stimulating factor-induced upregulation of Jak3 transcription during granulocytic differentiation is mediated by the cooperative action of Sp1 and Stat3

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