Abstract
TLR4 (Toll-like receptor 4) and B7-H1, which were known to be restricted to immune cells in the past, were found to be aberrantly expressed in a majority of tumor cells, facilitating tumor evasion from immune surveillance. Our study demonstrated that activation of TLR4 signaling in bladder cancer cells up-regulated B7-H1 expression. Furthermore, this regulation was significantly attenuated by ERK or JNK inhibitor. Our results elucidated the molecule mechanism of regulation of B7-H1 expression through TLR4 signaling and may suggest new strategies of down-regulating the cancer-associated B7-H1 expression for bladder cancer treatment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anthracenes / pharmacology
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Antigens, CD / biosynthesis*
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Antigens, CD / genetics
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B7-H1 Antigen
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Carcinoma, Transitional Cell / metabolism*
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Carcinoma, Transitional Cell / pathology
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Cell Line, Tumor
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Chromones / pharmacology
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / physiology
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Flavonoids / pharmacology
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Humans
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Imidazoles / pharmacology
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases / physiology
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Lipopolysaccharide Receptors / physiology
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Lipopolysaccharides / pharmacology
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology*
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Morpholines / pharmacology
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Phosphatidylinositol 3-Kinases / physiology
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation / drug effects
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Protein Kinase Inhibitors / pharmacology
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Protein Processing, Post-Translational / drug effects
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Proto-Oncogene Proteins c-akt / metabolism
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Pyridines / pharmacology
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Toll-Like Receptor 4 / physiology*
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Up-Regulation / drug effects
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Urinary Bladder Neoplasms / metabolism*
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Urinary Bladder Neoplasms / pathology
Substances
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Anthracenes
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Antigens, CD
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B7-H1 Antigen
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CD274 protein, human
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Chromones
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Flavonoids
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Imidazoles
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Lipopolysaccharide Receptors
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Lipopolysaccharides
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Morpholines
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Neoplasm Proteins
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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Pyridines
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TLR4 protein, human
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Toll-Like Receptor 4
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lipopolysaccharide, Escherichia coli O111 B4
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pyrazolanthrone
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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AKT1 protein, human
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one