Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | American Journal of Physiology: Gastrointestinal and Liver Physiology |
| Vol/bind | 290 |
| Udgave nummer | 1 |
| Sider (fra-til) | G120-8 |
| ISSN | 0193-1857 |
| DOI | |
| Status | Udgivet - 2005 |
Bibliografisk note
Keywords: Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Drug; Enzyme Activation; Gene Expression Regulation, Neoplastic; Hepatoblastoma; Humans; Mitogen-Activated Protein Kinase Kinases; NF-kappa B; Protein Binding; Proto-Oncogene Proteins; Receptors, Cytokine; Receptors, Thrombopoietin; Signal Transduction; ThrombopoietinAdgang til dokumentet
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I: American Journal of Physiology: Gastrointestinal and Liver Physiology, Bind 290, Nr. 1, 2005, s. G120-8.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Thrombopoietin stimulates migration and activates multiple signaling pathways in hepatoblastoma cells.
AU - Romanelli, Roberto G
AU - Petrai, Ilaria
AU - Robino, Gaia
AU - Efsen, Eva
AU - Novo, Erica
AU - Bonacchi, Andrea
AU - Pagliai, Gabriella
AU - Parola, Maurizio
AU - Navari, Nadia
AU - Delogu, Wanda
AU - Vizzutti, Francesco
AU - Rombouts, Krista
AU - Gentilini, Paolo
AU - Laffi, Giacomo
AU - Marra, Fabio
N1 - Keywords: Cell Line, Tumor; Cell Movement; Dose-Response Relationship, Drug; Enzyme Activation; Gene Expression Regulation, Neoplastic; Hepatoblastoma; Humans; Mitogen-Activated Protein Kinase Kinases; NF-kappa B; Protein Binding; Proto-Oncogene Proteins; Receptors, Cytokine; Receptors, Thrombopoietin; Signal Transduction; Thrombopoietin
PY - 2005
Y1 - 2005
N2 - Thrombopoietin (TPO), a cytokine that participates in the differentiation and maturation of megakaryocytes, is produced in the liver, but only limited information is available on the biological response of liver-derived cells to TPO. In this study, we investigated whether HepG2 cells express c-Mpl, the receptor for TPO, and whether TPO elicits biological responses and intracellular signaling in this cell type. Specific transcripts for c-Mpl were detected in HepG2 cells by RT-PCR, and expression of the protein was demonstrated by Western blot analysis and immunofluorescence. Exposure of HepG2 cells to TPO was associated with a dose-dependent increase in cell migration and chemoinvasion through Matrigel-coated filters. A checkerboard analysis showed that the effects of TPO on cell migration were dependent on both chemotaxis and chemokinesis. Exposure of HepG2 cells to TPO resulted in the activation of different members of the MAPK family, including ERK and JNK, as assessed using phosphorylation-specific antibodies and immune complex kinase assays. TPO also activated phosphatidylinositol 3-kinase (PI3K) and the downstream kinase Akt in a time-dependent manner. Finally, activation of c-Mpl was associated with increased activation of nuclear factor-kappaB. With the use of specific inhibitors, tyrosine phosphorylation and activation of PI3K were found to be required for the induction of migration in response to TPO. We conclude that TPO exerts biological actions on cultured hepatoblastoma cells via activation of c-Mpl and its downstream signaling.
AB - Thrombopoietin (TPO), a cytokine that participates in the differentiation and maturation of megakaryocytes, is produced in the liver, but only limited information is available on the biological response of liver-derived cells to TPO. In this study, we investigated whether HepG2 cells express c-Mpl, the receptor for TPO, and whether TPO elicits biological responses and intracellular signaling in this cell type. Specific transcripts for c-Mpl were detected in HepG2 cells by RT-PCR, and expression of the protein was demonstrated by Western blot analysis and immunofluorescence. Exposure of HepG2 cells to TPO was associated with a dose-dependent increase in cell migration and chemoinvasion through Matrigel-coated filters. A checkerboard analysis showed that the effects of TPO on cell migration were dependent on both chemotaxis and chemokinesis. Exposure of HepG2 cells to TPO resulted in the activation of different members of the MAPK family, including ERK and JNK, as assessed using phosphorylation-specific antibodies and immune complex kinase assays. TPO also activated phosphatidylinositol 3-kinase (PI3K) and the downstream kinase Akt in a time-dependent manner. Finally, activation of c-Mpl was associated with increased activation of nuclear factor-kappaB. With the use of specific inhibitors, tyrosine phosphorylation and activation of PI3K were found to be required for the induction of migration in response to TPO. We conclude that TPO exerts biological actions on cultured hepatoblastoma cells via activation of c-Mpl and its downstream signaling.
U2 - 10.1152/ajpgi.00350.2004
DO - 10.1152/ajpgi.00350.2004
M3 - Journal article
C2 - 16150872
SN - 0193-1857
VL - 290
SP - G120-8
JO - American Journal of Physiology: Gastrointestinal and Liver Physiology
JF - American Journal of Physiology: Gastrointestinal and Liver Physiology
IS - 1
ER -