UV light blocks EGFR signalling in human cancer cell lines.

UV light excites aromatic residues, causing these to disrupt nearby disulphide bridges. The EGF receptor is rich in aromatic residues near the disulphide bridges. Herein we show that laser-pulsed UV illumination of two different skin-derived cancer cell lines i.e. Cal-39 and A431, which both overexpress the EGF receptor, leads to arrest of the EGFR signaling pathway. The phosphorylation status of the receptor and the level of phosphorylated downstream signaling molecules i.e. AKT and the mitogen activated protein kinases (MAPKs) ERK1 and 2 is detected by Western blotting using phosphospecific antibodies. There was a threshold level, below which the receptor could not be blocked. In addition, illumination caused the cells to upregulate the cyclin-dependent kinase inhibitor p21WAF1, irrespective of the p53 status. Since the EGF receptor is often overexpressed in cancers and other proliferative skin disorders, it might be possible to significantly reduce the proliferative potential of these cells making them good targets for laser-pulsed UV light treatment.

[1]  M. Höpfner,et al.  Targeting the epidermal growth factor receptor by erlotinib (Tarceva™) for the treatment of esophageal cancer , 2006, International journal of cancer.

[2]  Xuejun Jiang,et al.  Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. , 2006, Molecular cell.

[3]  E. Baba,et al.  Gefitinib, a selective EGFR tyrosine kinase inhibitor, induces apoptosis through activation of Bax in human gallbladder adenocarcinoma cells , 2006, Journal of cellular biochemistry.

[4]  G. Tortora,et al.  Key cancer cell signal transduction pathways as therapeutic targets. , 2006, European journal of cancer.

[5]  M. T. Neves-Petersen,et al.  Photonic activation of disulfide bridges achieves oriented protein immobilization on biosensor surfaces , 2006, Protein science : a publication of the Protein Society.

[6]  S. Putta,et al.  Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor. , 2006, Carcinogenesis.

[7]  Chih-Hung Hsu,et al.  Inhibitors of Epidermoid Growth Factor Receptor Suppress Cell Growth and Enhance Chemosensitivity of Nasopharyngeal Cancer Cells in vitro , 2005, Oncology.

[8]  R. Tennant,et al.  Chemoprevention of UV light-induced skin tumorigenesis by inhibition of the epidermal growth factor receptor. , 2005, Cancer research.

[9]  James T. Elder,et al.  Antagonism of Epidermal Growth Factor Receptor Tyrosine Kinase Ameliorates the Psoriatic Phenotype in Organ-Cultured Skin , 2005, Skin Pharmacology and Physiology.

[10]  J. Baselga,et al.  Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  R. Eckert,et al.  Epigallocatechin-3-gallate Inhibits Epidermal Growth Factor Receptor Signaling Pathway , 2004, Journal of Biological Chemistry.

[12]  Yasuhiro Matsumura,et al.  Toxic effects of ultraviolet radiation on the skin. , 2004, Toxicology and applied pharmacology.

[13]  M. Ueda,et al.  Inhibition of the epidermal growth factor receptor suppresses telomerase activity in HSC-1 human cutaneous squamous cell carcinoma cells. , 2003, The Journal of investigative dermatology.

[14]  N. Magné,et al.  Molecular mechanisms underlying the interaction between ZD1839 (‘Iressa’) and cisplatin/5-fluorouracil , 2003, British Journal of Cancer.

[15]  C. Cordon-Cardo,et al.  Oncogenes in melanoma , 2003, Oncogene.

[16]  A. Abbruzzese,et al.  Critical role of both p27KIP1and p21CIP1/WAF1 in the antiproliferative effect of ZD1839 (‘Iressa’), an epidermal growth factor receptor tyrosine kinase inhibitor, in head and neck squamous carcinoma cells , 2003, Journal of cellular physiology.

[17]  P. Bertics,et al.  Caveolin-1 phosphorylation in human squamous and epidermoid carcinoma cells: dependence on ErbB1 expression and Src activation. , 2002, Experimental cell research.

[18]  J. V. Van Beeumen,et al.  Photoexcitation of tryptophan groups induces reduction of two disulfide bonds in goat alpha-lactalbumin. , 2002, Biochemistry.

[19]  R. K. Bright,et al.  The UV (Ribotoxic) Stress Response of Human Keratinocytes Involves the Unexpected Uncoupling of the Ras-Extracellular Signal-Regulated Kinase Signaling Cascade from the Activated Epidermal Growth Factor Receptor , 2002, Molecular and Cellular Biology.

[20]  A. Ullrich,et al.  A critical role for ras-mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. , 2002, Cancer research.

[21]  Zygmunt Gryczynski,et al.  High probability of disrupting a disulphide bridge mediated by an endogenous excited tryptophan residue , 2002, Protein science : a publication of the Protein Society.

[22]  T. Slaga,et al.  Functional roles of Akt signaling in mouse skin tumorigenesis , 2002, Oncogene.

[23]  R. Mason,et al.  Regulation of epidermal growth factor receptor expression in human melanocytes , 2001, Experimental dermatology.

[24]  C. Arteaga The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  S. Yonezawa,et al.  Expression of epithelial growth factor receptor and its two ligands, transforming growth factor-alpha and epithelial growth factor, in normal and neoplastic squamous cells in the vulva: an immunohistochemical study , 2001, Medical Electron Microscopy.

[26]  S. Katiyar A single physiologic dose of ultraviolet light exposure to human skin in vivo induces phosphorylation of epidermal growth factor receptor. , 2001, International journal of oncology.

[27]  Y. Yarden The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities. , 2001, European journal of cancer.

[28]  J. Voorhees,et al.  Ultraviolet irradiation activates PI 3-kinase/AKT survival pathway via EGF receptors in human skin in vivo. , 2001, International journal of oncology.

[29]  Y. Yarden,et al.  Untangling the ErbB signalling network , 2001, Nature Reviews Molecular Cell Biology.

[30]  John Mendelsohn,et al.  The EGF receptor family as targets for cancer therapy , 2000, Oncogene.

[31]  Fiona M. Watt,et al.  The EGF Receptor Provides an Essential Survival Signal for SOS-Dependent Skin Tumor Development , 2000, Cell.

[32]  Monilola A. Olayioye,et al.  The ErbB signaling network: receptor heterodimerization in development and cancer , 2000, The EMBO journal.

[33]  S. Yuspa,et al.  The epidermal growth factor receptor is required to maintain the proliferative population in the basal compartment of epidermal tumors. , 2000, Cancer research.

[34]  C. W. Hilbers,et al.  Tryptophan mediated photoreduction of disulfide bond causes unusual fluorescence behaviour of Fusarium solani pisi cutinase , 1999, FEBS letters.

[35]  S. Petersen,et al.  Amino acid neighbours and detailed conformational analysis of cysteines in proteins. , 1999, Protein engineering.

[36]  James M. Roberts,et al.  CDK inhibitors: positive and negative regulators of G1-phase progression. , 1999, Genes & development.

[37]  J. Woodburn,et al.  The epidermal growth factor receptor and its inhibition in cancer therapy. , 1999, Pharmacology & therapeutics.

[38]  X. F. Wang,et al.  UV radiation is a transcriptional inducer of p21(Cip1/Waf1) cyclin-kinase inhibitor in a p53-independent manner. , 1999, Experimental cell research.

[39]  T R Ioerger,et al.  Conservation of cys-cys trp structural triads and their geometry in the protein domains of immunoglobulin superfamily members. , 1999, Molecular immunology.

[40]  P. Heenan,et al.  Differential expression of epidermal growth factor receptor in melanocytic tumours demonstrated by immunohistochemistry and mRNA in situ hybridization , 1999, The Australasian journal of dermatology.

[41]  K. Kiguchi,et al.  Altered expression of epidermal growth factor receptor ligands in tumor promoter–treated mouse epidermis and in primary mouse skin tumors induced by an initiation‐promotion protocol , 1998, Molecular carcinogenesis.

[42]  D. Stern,et al.  Specificity within the EGF family/ErbB receptor family signaling network , 1998, BioEssays : news and reviews in molecular, cellular and developmental biology.

[43]  E. Adamson,et al.  UV activates growth factor receptors via reactive oxygen intermediates , 1996, The Journal of cell biology.

[44]  J. Bos,et al.  UV activation of receptor tyrosine kinase activity. , 1995, Oncogene.

[45]  I. Gimenez-Conti,et al.  Altered expression of the epidermal growth factor receptor and transforming growth factor‐α during multistage skin carcinogenesis in SENCAR mice , 1994, Molecular carcinogenesis.

[46]  D. Givol,et al.  Induction of WAF1/CIP1 by a p53-independent pathway. , 1994, Cancer research.

[47]  V. Deleo,et al.  Ultraviolet radiation induces phosphorylation of the epidermal growth factor receptor. , 1994, Cancer research.

[48]  G. Clinton,et al.  Antibodies against highly conserved sites in the epidermal growth factor receptor tyrosine kinase domain as probes for structure and function. , 1993, Biochemistry.

[49]  D. Macdonald,et al.  Abnormal expression of epidermal growth factor receptor in cutaneous epithelial tumours , 1992, Journal of cutaneous pathology.

[50]  K. Ellem,et al.  UVC modulation of epidermal growth factor receptor number in HeLa S3 cells. , 1992, Carcinogenesis.

[51]  D. Clarke-Pearson,et al.  Expression of epidermal growth factor receptor and HER‐2/neu in normal and neoplastic cervix, vulva, and vagina , 1990, Obstetrics and gynecology.

[52]  K. Ellem,et al.  UVR induction of TGF alpha: a possible autocrine mechanism for the epidermal melanocytic response and for promotion of epidermal carcinogenesis. , 1988, Carcinogenesis.

[53]  I. Pastan,et al.  Hyperproduction and gene amplification of the epidermal growth factor receptor in squamous cell carcinomas. , 1985, Japanese journal of cancer research : Gann.

[54]  D. Connolly,et al.  Synthesis, turnover, and down-regulation of epidermal growth factor receptors in human A431 epidermoid carcinoma cells and skin fibroblasts. , 1982, The Journal of biological chemistry.

[55]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[56]  E. Efstathiou,et al.  Exacerbation of psoriasis after treatment with an EGFR tyrosine kinase inhibitor. , 2004, Acta dermato-venereologica.

[57]  J. Utikal,et al.  Chromosome 7 aneusomy. A marker for metastatic melanoma? Expression of the epidermal growth factor receptor gene and chromosome 7 aneusomy in nevi, primary malignant melanomas and metastases. , 2001, Neoplasia.

[58]  M. Reiss,et al.  Status of the p53 tumor suppressor gene in human squamous carcinoma cell lines. , 1992, Oncology research.