Role of protein kinase C in expression of granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor in lung cancer cells
We examine the role of protein kinase C (PKC) pathways in the constitutive expression of granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) in lung cancer cells. Two cell lines, OKa-C-1 and MI-4, constitutively produce an abundant dose of G-CSF and GM-CSF. The PKC activator phorbol 12-myristate 13-acetate (PMA) stimulated the production of GM-CSF in a dose-dependent manner and reduced G-CSF in the cell lines. The PKC inhibitor staurosporine had effects opposite to those of PMA in the cell lines. Another PKC activator (4β-phorbol 12, 13-dibutyrate) and six specific PKC inhibitors (bisindolylmaleimide I, calphostin C, chelerythrine chloride, Gö 6976, PKC inhibitor 19-27, and Ro-32-0432) also worked as well as PMA and staurosporine, respectively. The induction of GM-CSF expression via PKC activation was mediated by the activation of nuclear factor-κB. The induction of G-CSF expression via PKC inhibition was mediated by p44/42 mitogen-activated protein kinase and c-Jun N-terminal kinase pathway signaling. GM-CSF may accelerate cell growth and inhibit cell death via PKC activation in the cell lines. G-CSF also seems to reverse growth suppression and cell death induced by PKC inhibition.
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Document Type: Research Article
Affiliations: Department of Internal Medicine, Kochi Medical School, Kochi 783-8505, Japan, Email: [email protected]
Publication date: November 1, 2005
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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