Abstract
We previously established 2 lung cancer cell lines, OKa-C-1 and MI-4, which constitutively produce an abundant dose of granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF). Many other cases with G-CSF or GM-CSF producing tumors have been reported up to the present. However, the biological properties of the overproduction of G-CSF and GM-CSF by tumor cells have not been well known. Several reports demonstrated the presence of an autocrine growth loop for G-CSF and GM-CSF in nonhematopoietic tumor cells. We showed that exogenous G-CSF and GM-CSF stimulated cell growth in a dose-dependent manner in OKa-C-1 and MI-4 cells. We could detect the presence of G-CSF and GM-CSF receptors in both cell lines by RT-PCR analysis. We have previously shown that inflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta enhance the expression of G-CSF and GM-CSF in the cell lines. However, the factors that regulate constitutive production of G-CSF or GM-CSF by tumor cells are still unknown well. In our study, we first reported that serum deprivation stimulated constitutive production of G-CSF and GM-CSF by lung tumor cells through activation of nuclear factor (NF)-kappaB and p44/42 mitogen-activated protein kinase (MAPK) pathway signaling. We suggest that G-CSF and GM-CSF constitutively produced by tumor cells could grow tumor itself and rescue tumor cells from the cytotoxicity of serum deprivation.
Copyright 2004 Wiley-Liss, Inc.
MeSH terms
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Carcinoma, Large Cell / metabolism*
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Carcinoma, Large Cell / pathology
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Carcinoma, Squamous Cell / metabolism*
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Carcinoma, Squamous Cell / pathology
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Cell Division
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Culture Media, Serum-Free
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Granulocyte Colony-Stimulating Factor / biosynthesis*
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
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Humans
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Interleukin-1 / pharmacology
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Lung Neoplasms / metabolism*
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Lung Neoplasms / pathology
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Granulocyte Colony-Stimulating Factor / metabolism
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Recombinant Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Culture Media, Serum-Free
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Interleukin-1
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NF-kappa B
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RNA, Messenger
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Receptors, Granulocyte Colony-Stimulating Factor
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Granulocyte Colony-Stimulating Factor
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Granulocyte-Macrophage Colony-Stimulating Factor
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases