Abstract
Proteins involved in the visual signaling cascade show light-dependent expression levels in photoreceptor cells. Recently, these proteins have been described to be expressed in neuroectodermal tumors and to function as cancer-retina antigens. Here, we show that light can down-regulate gene expression of rhodopsin, transducin, and cyclic guanosine 3',5'-monophosphate phosphodiesterase 6 (PDE6) and up-regulate guanylyl cyclase 1, recoverin, and arrestin in human melanoma cells in vitro, comparable to physiologic changes earlier observed in photoreceptor cells. Similar modulation can be detected at the protein level in melanoma cells except for no changes in PDE6 protein levels. Two regulatory pathways have been identified: Sp1/Sp3/Sp4 proteins for rhodopsin and PDE6, and mitogen-activated protein kinases for recoverin and arrestin. The visual cascade and retinoic acid as its derivate do not play any role in this process. Putative explanations for light-dependent modulation of cancer-retina antigen expression in melanoma cells are discussed.
MeSH terms
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Antigens, Neoplasm / genetics*
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Antigens, Neoplasm / metabolism
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Butadienes / pharmacology
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Cell Line, Tumor
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Cyclic Nucleotide Phosphodiesterases, Type 6 / metabolism
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Down-Regulation / drug effects
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Down-Regulation / radiation effects
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Epithelial Cells / radiation effects
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Eye Proteins / genetics*
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Eye Proteins / metabolism
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / radiation effects*
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Humans
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Light*
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Melanocytes / drug effects
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Melanocytes / metabolism
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Melanocytes / radiation effects
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Models, Biological
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Nitriles / pharmacology
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Photoreceptor Cells / drug effects
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Photoreceptor Cells / metabolism
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Photoreceptor Cells / radiation effects
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / radiation effects
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Proto-Oncogene Proteins c-fos / metabolism
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Proto-Oncogene Proteins c-jun / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Sp Transcription Factors / genetics
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Sp Transcription Factors / metabolism
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Tretinoin / pharmacology
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Vision, Ocular / drug effects
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Vision, Ocular / radiation effects
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rho GTP-Binding Proteins / metabolism
Substances
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Antigens, Neoplasm
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Butadienes
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Eye Proteins
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Nitriles
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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RNA, Messenger
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Sp Transcription Factors
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U 0126
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Tretinoin
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Cyclic Nucleotide Phosphodiesterases, Type 6
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rho GTP-Binding Proteins