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Signaling and Regulation

Visible Light Modulates the Expression of Cancer-Retina Antigens

¹ Skin Cancer Unit, German Cancer Research Center; ² Division of Toxicology and Cancer Risk Factors, German Cancer Research Center, Heidelberg, Germany; ³ University Hospital Mannheim, Mannheim, Germany; and ⁴ Department of Cell Signalling, A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Moscow, Russia

Requests for reprints: Alexandr Bazhin or Stefan Eichmüller, Skin Cancer Unit (G300), German Cancer Research Center, Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany. Phone: 49-6221-423354/80; Fax: 49-6221-423379. E-mail: a.bazhin{at}dkfz.de or s.eichmueller{at}dkfz.de

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. (Mol Cancer Res 2008;6(1):110–8)