Visible light modulates the expression of cancer-retina antigens.
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.
Bazhin
Alexandr V
AV
Skin Cancer Unit, German Cancer Research Center, Im Neuenheimer Feld 580, Heidelberg, Germany. a.bazhin@dkfz.de
Schadendorf
Dirk
D
Owen
Robert W
RW
Zernii
Evgeni Yu
EY
Philippov
Pavel P
PP
Eichmüller
Stefan B
SB
D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D008027:Light; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008954:Models, Biological; D009570:Nitriles / Q000494:pharmacology; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014176:Protein Biosynthesis / Q000187:drug effects / Q000528:radiation effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051703:Sp Transcription Factors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014785:Vision, Ocular / Q000187:drug effects / Q000528:radiation effects; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000951:Antigens, Neoplasm; D002070:Butadienes; D005136:Eye Proteins; D009570:Nitriles; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D051703:Sp Transcription Factors; C113580:U 0126; D014212:Tretinoin; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D020741:rho GTP-Binding Proteins