Publication: Thrombopoietin (TPO) induces c-myc expression through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKC<inf>ζ</inf>or mTOR in TPO-dependent cell lines and primary megakaryocytes
Issued Date
2006-08-01
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ISSN
08986568
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2-s2.0-33646364562
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Mahidol University
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SCOPUS
Bibliographic Citation
Cellular Signalling. Vol.18, No.8 (2006), 1212-1218
Suggested Citation
Supantitra Chanprasert, Amy E. Geddis, Charlene Barroga, Norma E. Fox, Kenneth Kaushansky Thrombopoietin (TPO) induces c-myc expression through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKC<inf>ζ</inf>or mTOR in TPO-dependent cell lines and primary megakaryocytes. Cellular Signalling. Vol.18, No.8 (2006), 1212-1218. doi:10.1016/j.cellsig.2005.09.010 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/23001
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Title
Thrombopoietin (TPO) induces c-myc expression through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKC<inf>ζ</inf>or mTOR in TPO-dependent cell lines and primary megakaryocytes
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Abstract
Thrombopoietin (TPO) and its receptor (c-Mpl) are the major regulators of megakaryocyte and platelet production and serve a critical and non-redundant role in hematopoietic stem cell (HSC) biology. TPO signals through the Jak-STAT, Ras-Raf-MAPK, and PI3K pathways, and promotes survival, proliferation, and polyploidization in megakaryocytes. The proto-oncogene c-myc also plays an important role in many of these same processes. In this work we studied the regulated expression of c-myc in megakaryocytic cell lines and primary cells by quantitative real-time RT-PCR. We found that TPO induced expression of c-myc in 1 h in both hematopoietic cell lines (UT-7 and BaF3/Mpl) and mature murine megakaryocytes. The TPO-induced expression of c-myc was blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor, suggesting that TPO stimulated c-myc expression through a PI3K-dependent pathway. Of interest, our study showed that overexpression of active Akt did not rescue the effect of PI3K blockade on c-myc expression, rather, enhanced it. In addition, inhibitors of protein kinase C (PKC)ζand the target of rapamycin (mTOR) also failed to affect c-myc mRNA expression, while c-myc mRNA expression was reduced by inhibition of the mitogen activated protein kinase (MAPK) pathway. Therefore, we conclude that TPO stimulates c-myc expression in primary megakaryocytes through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKCζor mTOR. © 2005 Elsevier Inc. All rights reserved.