Abstract
Constitutive overexpression of cyclooxygenase-2 (COX-2) occurs frequently in several different malignancies, including lung, colon, breast, and prostate cancer. Clinical studies have established elevated serum insulin-like growth factor (IGF-I) content and IGF-I:IGF-binding protein 3 (IGFBP-3) ratio as risk factors for these same malignancies. Therefore, we sought to determine the link between COX-2 expression and the IGF axis in COX-2 gene-modified human non-small-cell lung cancer (NSCLC) cells. Overexpression of COX-2 in NSCLC cells enhanced the antiapoptotic and mitogenic effects of IGF-I and IGF-II, facilitated the autophosphorylation of the type 1 IGF receptor, increased class IA phosphatidylinositol 3'-kinase activity, and decreased expression of IGFBP-3. Thus, these findings show that COX-2 augments the stimulatory arm of the IGF axis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis / physiology
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Carcinoma, Non-Small-Cell Lung / enzymology*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Celecoxib
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Cell Division / physiology
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Cell Line, Tumor
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Cell Survival / physiology
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Cyclooxygenase 2
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DNA, Antisense / genetics
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Down-Regulation / drug effects
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Humans
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Insulin-Like Growth Factor Binding Protein 3 / biosynthesis
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Insulin-Like Growth Factor I / pharmacology
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Insulin-Like Growth Factor I / physiology*
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Insulin-Like Growth Factor II / pharmacology
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Insulin-Like Growth Factor II / physiology*
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / biosynthesis
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Isoenzymes / genetics
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Isoenzymes / physiology*
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Lung Neoplasms / enzymology*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Membrane Proteins
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation
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Prostaglandin-Endoperoxide Synthases / biosynthesis
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Prostaglandin-Endoperoxide Synthases / genetics
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Prostaglandin-Endoperoxide Synthases / physiology*
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Pyrazoles
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Receptor, IGF Type 1 / metabolism*
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Signal Transduction / physiology
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Sulfonamides / pharmacology
Substances
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DNA, Antisense
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Insulin-Like Growth Factor Binding Protein 3
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Isoenzymes
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Membrane Proteins
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Phosphoinositide-3 Kinase Inhibitors
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Pyrazoles
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Sulfonamides
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Insulin-Like Growth Factor I
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Insulin-Like Growth Factor II
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Receptor, IGF Type 1
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Celecoxib