Role of tumor necrosis factor-α in the regulation of keratinocyte cell cycle and DNA repair after ultraviolet-b radiation

Danish Medical Bulletin

Volumn 57, Issue 10, 2010, Pages

  Faurschou, Annesofie ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; INFLIXIMAB; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN BAD; PROTEIN KINASE B; PROTEIN KINASE C; TRANSCRIPTION FACTOR FKHRL1; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; APOPTOSIS REGULATORY PROTEIN; DERMATOLOGICAL AGENT; MONOCLONAL ANTIBODY; REACTIVE OXYGEN METABOLITE; TUMOR NECROSIS FACTOR RECEPTOR;

APOPTOSIS; ARTICLE; AUTOIMMUNE DISEASE; CELL CYCLE ARREST; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE PROGRESSION; CELL CYCLE REGULATION; CONTROLLED STUDY; DNA REPAIR; HUMAN; HUMAN CELL; KERATINOCYTE; MUTATION; PRECANCER; SKIN CANCER; SKIN CARCINOGENESIS; ULTRAVIOLET B RADIATION; CELL CYCLE; CYTOLOGY; DNA DAMAGE; GENETICS; PHYSIOLOGY; RADIATION EXPOSURE; REVIEW; SIGNAL TRANSDUCTION; ULTRAVIOLET RADIATION;

ANTIBODIES, MONOCLONAL; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; CELL CYCLE; DERMATOLOGIC AGENTS; DNA DAMAGE; DNA REPAIR; HUMANS; KERATINOCYTES; REACTIVE OXYGEN SPECIES; RECEPTORS, TUMOR NECROSIS FACTOR; SIGNAL TRANSDUCTION; TUMOR NECROSIS FACTOR-ALPHA; ULTRAVIOLET RAYS;

EID: 79251506315     PISSN: 16039629     EISSN: 16039629     Source Type: Journal    
DOI: None     Document Type: Article

References (103)

1. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) Endotoxin-lnduced Serum Factor That Causes Necrosis of Tumors. Proceedings of the National Academy of Sciences of the United States of America 72:3666-3670
2. Infante-Duarte C, Horton HF, Byrne MC, Kamradt T (2000) Microbial lipopeptides induce the production of IL-17 in Th cells. Journal of Immunology 165:6107-15
3. Schmidt-Weber CB, Akdis M, Akdis CA (2007) TH17 cells in the big picture of immunology. Journal of Allergy and Clinical Immunology 120:247-254
4. Kock A, Schwarz T, Kirnbauer R, Urbanski A, Perry P, Ansel JC, Luger TA (1990) Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light. Journal of Experimental Medicine 172:1609-1614
5. Skov L, Hansen H, Allen M, Villadsen L, Norval M, Barker JN, Simon J, Baadsgaard O. (1998) Contrasting effects of ultraviolet A1 and ultraviolet B exposure on the induction of tumor necrosis factor-alpha in human skin. British Journal of Dermatology 138:216-220
6. Trefzer U, Brockhaus M, Lotscher H, Parlow F, Budnik A, Grewe M, Christoph H, Kapp A, Schopf E, Luger TA, Krutmann J (1993) The 55-Kd Tumor-Necrosis-Factor Receptor on Human Keratinocytes Is Regulated by Tumor-Necrosis-Factor-Alpha and by Ultraviolet-B Radiation. Journal of Clinical Investigation 92:462-470
7. Micheau O, Tschopp J (2003) Induction of TNF receptor l-mediated apoptosis via two sequential signaling complexes. Cell 114:181-190
8. Muppidi JR, Tschopp J, Siegel RM (2004) Life and death decisions: secondary complexes and lipid rafts in TNF receptor family signal transduction. Immunity 21:461-465
9. Gisondi P, Gubinelli E, Cocuroccia B, Girolomoni G (2004) Targeting tumor necrosis factor-alpha in the therapy of psoriasis. Current Drug Targets - Inflammation & Allergy 3:175-183
10. Tobin AM, Kirby B (2005) TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis. BioDrugs 19:47-57
11. Reguiai Z, Grange F (2007) The role of anti-tumor necrosis factor-alpha therapy in Pyoderma gangrenosum associated with inflammatory bowel disease. American Journal of Clinical Dermatology 8:67-77
12. Old LJ (1988) Tumor Necrosis Factor. Scientific American 258:59
13. Asher AL, Mule JJ, Kasid A, Restifo NP, Salo JC, Rei-chert CM, Jaffe G, Fendly B, Kriegler M, Rosenberg SA (1991) Murine tumor cells transduced with the gene for tumor necrosis factor-alpha. Evidence for paracrine immune effects of tumor necrosis factor against tumors. Journal of Immunology 146:3227-3234
14. Zhuang L, Wang B, Shinder GA, Shivji GM, Mak TW, Sauder DN (1999) TNF receptor p55 plays a pivotal role in murine keratinocyte apoptosis induced by. ultraviolet B irradiation. Journal of Immunology 162:1440-1447
15. Schwarz A, Bhardwaj R, Aragane Y, Mahnke K, Rie-mann H, Metze D, Luger TA, Schwarz T (1995) Ultra-violet-B-induced apoptosis of keratinocytes: evidence for partial involvement of tumor necrosis factor-alpha in the formation of sunburn cells. Journal of Investigative Dermatology 104:922-927
16. Suganuma M, Okabe S, Marino MW, Sakai A, Sueoka E, Fujiki H (1999) Essential role of tumor necrosis factor alpha (TNP-alpha) in tumor promotion as revealed by TNF-alpha-deficient mice. Cancer Research 59:4516-4518
17. Arnott CH, Scott KA, Moore RJ, Robinson SC, Thompson RG, Balkwill FR (2004) Expression of both TNF-alpha receptor subtypes is essential for optimal skin tumor development. Oncogene 23:1902-1910
18. Moore RJ, Owens DM, Stamp G, Arnott C, Burke F, East N, Holdsworth H, Turner L, Rollins B, Pasparakis M, Kollias G, Balkwill F (1999) Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nature Medicine 5:828-831
19. Loercher A, Lee TL, Ricker JL, Howard A, Geoghegen J, Chen Z, Sunwoo JB, Sitcheran R, Chuang EY, Mitchell JB, Baldwin AS, Jr., Van Waes C (2004) Nuclear factor-kappaB is an important modulator of the altered gene expression profile and malignant phenotype in squamous cell carcinoma. Cancer Research 64:6511-6523
20. Duffey DC, Chen Z, Dong G, Ondrey FG, Wolf JS, Brown K, Siebenlist U, Van Waes C (1999) Expression of a dominant-negative mutant inhibitor-kappaBalpha of nuclear factor-kappaB in human head and neck squamous cell carcinoma inhibits survival, proinflammatory cytokine expression, and tumor growth in vivo. Cancer Research 59:3468-3474
21. Dajee M, Lazarov M, Zhang JY, Cai T, Green CL, Russell AJ, Marinkovich MP, Tao S, Lin Q, Kubo Y, Khavari PA (2003) NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Nature 421:639-643
22. Jackson-Bernitsas DG, Ichikawa H, Takada Y, Myers JN, Lin XL, Darnay BG, Chaturvedi MM, Aggarwal BB (2007) Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF-kappaB activation and proliferation in human head and neck squamous cell carcinoma. Oncogene 26:1385-1397
23. Seitz CS, Deng H, Hinata K, Lin Q, Khavari PA (2000) Nuclear factor kappaB subunits induce epithelial cell growth arrest. Cancer Research 60:4085-4092
24. Ren Q, Kari C, Quadras MR, Burd R, McCue P, Dicker AP, Rodeck U (2006) Malignant transformation of immortalized HaCaT keratinocytes through deregulated nuclear factor kappaB signaling. Cancer Research 66:5209-5215
25. Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS, Jr. (1998) NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAPl and C-IAP2 to suppress caspase-8 activation. Science 281:1680-1683
26. Wang CY, Cusack JC, Jr., Liu R, Baldwin AS, Jr. (1999) Control of inducible chemoresistance: enhanced antitumor therapy through increased apoptosis by inhibition of NF-kappaB. Nature Medicine 5:412-417
27. Karin M, Cao Y, Greten FR, Li ZW (2002) NF-kappaB in cancer: from innocent bystander to major culprit. Nature Reviews Cancer 2:301-310
28. Basile JR, Eichten A, Zacny V, Munger K (2003) NF-kappaB-mediated induction of p21(Cipl/Wafl) by tumor necrosis factor alpha induces growth arrest and cytoprotection in normal human keratinocytes. Molecular Cancer Research 1:262-270
29. Vasudevan KM, Gurumurthy S, Rangnekar VM (2004) Suppression of PTEN expression by NF-kappa B prevents apoptosis. Molecular and Cellular Biology 24:1007-1021
30. Kim S, Domon-Dell C, Kang J, Chung DH, Freund JN, Evers BM (2004) Down-regulation of the tumor suppressor PTEN by the tumor necrosis factor-alpha/nuclear factor-kappaB (NF-kappaB)-inducing ki-nase/NF-kappaB pathway is linked to a default Ikap-paB-alpha autoregulatory loop. Journal of Biological Chemistry 279:4285-4291
31. Zhang QS, Maddock DA, Chen JP, Heo S, Chiu C, Lai D, Souza K, Mehta S, Wan YS (2001) Cytokine-induced p38 activation feedback regulates the prolonged activation of AKT cell survival pathway initiated by reactive oxygen species in response to UV irradiation in human keratinocytes. International Journal of Oncology 19:105710-61
32. Janes KA, Gaudet S, Albeck JG, Nielsen UB, Lauffen-burger DA, Sorger PK (2006) The response of human epithelial cells to TNF involves an inducible autocrine cascade. Cell 124:1225-1239
33. Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB (1999) NF-kappaB activation by tumor necrosis factor requires the Akt serine-threonine kinase. Nature 401:82-85
34. Chakravarty EF, Michaud K, Wolf F (2004) Incidence of skin cancer in patients with rheumatoid arthritis. Arthritis and Rheumatism 50:S558-S559
35. Faurschou M, Sorensen IJ, Mellemkjaer L, Loft AGR, Thomsen BS, Tvede N, Baslund B (2008) Malignancies in Wegener's granulomatosis: Incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. Journal of Rheumatology 35:100-105
36. Lindelof B, Sigurgeirsson B, Gabel H, Stern RS (2000) Incidence of skin cancer in 5356 patients following organ transplantation. British Journal of Dermatology 143:513-519
37. Moloney FJ, Comber H, O'Lorcain P, O'Kelly P, Conlon PJ, Murphy GM (2006) A population-based study of skin cancer incidence and prevalence in renal transplant recipients. British Journal of Dermatology 154:498-504
38. Courdavault S, Baudouin C, Charveron M, Canguilhem B, Favier A, Cadet J, Douki T (2005) Repair of the three main types of bipyrimidine DNA photoproducts in human keratinocytes exposed to UVB and UVA radiations. DNA Repair 4:836-844
39. Chouinard N, Therrien JP, Mitchell DL, Robert M, Drouin R, Rouabhia M (2001) Repeated exposures of human skin equivalent to low doses of ultraviolet-B radiation lead to changes in cellular functions and accumulation of cyclobutane pyrimidine dimers. Biochemistry and Cell Biology-Biochimie et Biologie Cellu-laire 79:507-515
40. You YH, Lee DH, Yoon JH, Nakajima S, Yasui A, Pfeifer GP (2001) Cyclobutane pyrimidine dimers are responsible for the vast majority of mutations induced by UVB irradiation in mammalian cells. Journal of Biological Chemistry 276:44688-44694
41. Kripke ML, Cox PA, Alas LG, Yarosh DB (1992) Pyrimidine Dimers in Dna Initiate Systemic Immunosuppression in Uv-lrradiated Mice. Proceedings of the National Academy of Sciences of the United States of America 89:7516-7520
42. Nishigori C, Yarosh DB, Donawho C, Kripke ML (1996) The immune system in ultraviolet carcinogenesis. Journal of Investigative Dermatology Symposium Proceedings 1:143-146
43. Brash DE, Ziegler A, Jonason AS, Simon JA, Kunala S, Leffell DJ (1996) Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion. Journal of Investigative Dermatology Symposium Proceedings 1:136-142
44. Balajee AS, Bohr VA (2000) Genomic heterogeneity of nucleotide excision repair. Gene 250:15-30
45. Dworaczek H, Xiao W (2007) Xeroderma pigmentosum: a glimpse into nucleotide excision repair, genetic instability, and cancer. Critical Reviews in Oncogenesis 13:159-177
46. Wang LE, Xiong P, Strom SS, Goldberg LH, Lee JE, Ross Ml, Mansfield PF, Gershenwald JE, Prieto VG, Cormier JN, Duvic M, dayman GL, Weber RS, Lippman SM, Amos CI, Spitz MR, Wei Q (2005) In vitro sensitivity to ultraviolet B light and skin cancer risk: a case-control analysis. Journal of the National Cancer Institute 97:1822-18231
47. Abraham RT (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes & Development 15:2177-2196
48. Hiramatsu K, Ogino T, Ozaki M, Okada S (2006) Mo-nochloramine inhibits ultraviolet B-induced p53 activation and DNA repair response in human fibroblasts. Biochimica et Biophysica Acta-Molecular Cell Research 1763:188-196
49. Bulavin DV, Higashimoto Y, Popoff IJ, Gaarde WA, Ba-srur V, Potapova 0, Appella E, Fornace AJ (2001) Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase. Nature 411:102-107
50. Sun H, Lesche R, Li DM, Liliental J, Zhang H, Gao J, Ga-vrilova N, Mueller B, Liu X, Wu H (1999) PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proceedings of the National Academy of Sciences of the United States of America 96:6199-6204
51. Henry MK, Lynch JT, Eapen AK, Quelle FW (2001) DNA damage-induced cell-cycle arrest of hematopoietic cells is overridden by activation of the PI-3 kinase/Akt signaling pathway. Blood 98:834-841
52. Kandel ES, Skeen J, Majewski N, Di Cristofano A, Pan-dolfi PP, Feliciano CS, Gartel A, Hay N (2002) Activation of Akt/protein kinase B overcomes a G(2)/m cell cycle checkpoint induced by DNA damage. Molecular and Cellular Biology 22:7831-7841
53. Greer EL, Brunet A (2005) FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24:7410-7425
54. Medema RH, Kops GJ, Bos JL, Burgering BM (2000) AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kipl. Nature 404:782-787
55. Tran H, Brunet A, Grenier JM, Datta SR, Fornace AJ, Jr., DiStefano PS, Chiang LW, Greenberg ME (2002) DNA repair pathway stimulated by the forkhead transcription factor FOX03a through the Gadd45 protein. Science 296:530-534
56. Ramaswamy S, Nakamura N, Sansal I, Bergeron L, Sellers WR (2002) A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR. Cancer Cell 2:81-91
57. You H, Yamamoto K, Mak TW (2006) Regulation of transactivation-independent proapoptotic activity of p53 by FOX03a. Proc Natl Acad Sci U S A 103:9051-9056
58. Barthel A, Schmoll D, Unterman TG (2005) FoxO proteins in insulin action and metabolism. Trends in Endocrinology and Metabolism 16:183-189
59. Dijkers PF, Medema RH, Lammers JW, Koenderman L, Coffer PJ (2000) Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1. Current Biology 10:1201-1204
60. Tang TT, Dowbenko D, Jackson A, Toney L, Lewin DA, Dent AL, Lasky LA (2002) The forkhead transcription factor AFX activates apoptosis by induction of the BCL-6 transcriptional repressor. Journal of Biological Chemistry 277:14255-14265
61. Engstrom M, Karlsson R, Jonsson Jl (2003) Inactivation of the forkhead transcription factor Fox03 is essential for PKB-mediated survival of hematopoietic progenitor cells by kit ligand. Experimental Hematology 31:316-323
62. Cohen JJ (1993) Apoptosis. Immunology Today 14:126-130
63. Murphy G, Young AR, Wulf HC, Kulms D, Schwarz T (2001) The molecular determinants of sunburn cell formation. Experimental Dermatology 10:155-160
64. Schultz DR, Harrington WJ (2003) Apoptosis: Programmed cell death at a molecular level. Seminars in Arthritis and Rheumatism 32:345-369
65. Takasawa R, Nakamura H, Mori T, Tanuma S (2005) Differential apoptotic pathways in human keratino-cyte HaCaT cells exposed to UVB and UVC. Apoptosis 10:1121-30
66. Datta SR, Brunet A, Greenberg ME (1999) Cellular survival: a play in three Akts. Genes & Development 13:2905-2927
67. Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ (1996) Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell 87:619-268
68. Henseleit U, Zhang J, Wanner R, Haase I, Kolde G, Ro-senbach T (1997) Role of p53 in UVB-induced apoptosis in human HaCaT keratinocytes. Journal of Investigative Dermatology 109:722-727
69. Mitoma H, Horiuchi T, Hatta N, Tsukamoto H, Hara-shima S, Kikuchi Y, Otsuka J, Okamura S, Fujita S, Harada M (2005) Infliximab induces potent antiinflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology 128:376-392
70. Lugering A, Schmidt M, Lugering N, Pauels HG, Domschke W, Kucharzik T (2001) Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway. Gastroenterology 121:1145-1157
71. ten Hove T, Van Montfrans C, Peppelenbosch MP, Van Deventer SJH (2002) Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn's disease. Gut 50:206-211
72. Van den Brande JMH, Braat H, Van Den Brink GR, Versteeg HH, Bauer CA, Hoedemaeker I, Van Montfrans C, Hommes DW, Peppelenbosch MP, Van Deventer SJH (2003) Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology 124:1774-1785
73. Segrelles C, Moral M, Lara MF, Ruiz S, Santos M, Leis H, Garcia-Escudero R, Martinez-Cruz AB, Martinez-Palacio J, Hernandez P, Ballestin C, Paramio JM (2006) Molecular determinants of Akt-induced keratinocyte transformation. Oncogene 25:1174-1185
74. Suzuki A, Itami S, Ohishi M, Hamada K, Inoue T, Koma-zawa N, Senoo H, Sasaki T, Takeda J, Manabe M, Mak TW, Nakano T (2003) Keratinocyte-specific PTEN deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation. Cancer Research 63:674-681
75. Altomare DA, Testa JR (2005) Perturbations of the AKT signaling pathway in human cancer. Oncogene 24:7455-7464
76. Alessi DR, Deak M, Casamayor A, Caudwell FB, Mor-rice N, Norman DG, Gaffney P, Reese CB, MacDougall CN, Harbison D, Ashworth A, Bownes M (1997) 3-phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophi-la DSTPK61 kinase. Current Biology 7:776-789
77. Cantley LC, Neel BG (1999) New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase AKT pathway. Proceedings of the National Academy of Sciences of the United States of America 96:4240-4245
78. Wang HQ, Quan T, He T, Franke TF, Voorhees JJ, Fisher GJ (2003) Epidermal growth factor receptor-dependent, NF-kappaB-independent activation of the phosphatidylinositol 3-kinase/Akt pathway inhibits ultraviolet irradiation-induced caspases-3, -8, and -9 in human keratinocytes. Journal of Biological Chemistry 278:45737-45745
79. Lisby S, Faurschou A, Gniadecki R (2007) The autocrine TNFalpha signaling loop in keratinocytes requires atypical PKC species and NF-kappaB activation but is independent of cholesterol-enriched membrane mi-crodomains. Biochemical Pharmacology 15;73(4):526-533
80. Moscat J, Diaz-Meco MT (2000) The atypical protein kinase Cs - Functional specificity mediated by specific protein adapters. Embo Reports 1:399-403
81. Nesterov A, Lu XJ, Johnson M, Miller GJ, Ivashchenko Y, Kraft AS (2001) Elevated Akt activity protects the prostate cancer cell line LNCaP from TRAIL-induced apoptosis. Journal of Biological Chemistry 276:10767-10774
82. Chen X, Thakkar H, Tyan F, Gim S, Robinson H, Lee C, Pandey SK, Nwokorie C, Onwudiwe N, Srivastava RK (2001) Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer. Oncogene 20:6073-6083
83. Fruehauf JP, Meyskens FL (2007) Reactive oxygen species: A breath of life or death? Clinical Cancer Research 13:789-794
84. Jamaluddin M, Wang SF, Boldogh I, Tian B, Brasier AR (2007)TNF-alpha-induced NF-kappa B/RelA Ser(276) phosphorylation and enhanceosome formation is mediated by an ROS-dependent PKAc pathway. Cellular Signaling 19:1419-1433
85. Aruoma OL, Halliwell B, Hoey BM, Butler J (1989) The Antioxidant Action of N-Acetylcysteine - Its Reaction with Hydrogen-Peroxide, Hydroxyl Radical, Superoxide, and Hypochlorous Acid. Free Radical Biology and Medicine 6:593-597
86. Harada D, Naito S, Hiraoka I, Otagiri M (2002) In vivo kinetic analysis of covalent binding between N-acetyl-L-cysteine and plasma protein through the formation of mixed disulfide in rats. Pharmaceutical Research 19:615-620
87. Halliwell B (1989) Protection against tissue damage in vivo by desferrioxamine: what is its mechanism of action? Free Radical Biology & Medicine 7:645-651
88. Chang F, Steelman LS, Lee JT, Shelton JG, Navolanic PM, Blalock WL, Franklin RA, McCubrey JA (2003) Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 17:1263-1293
89. Albanell J, Codony-Servat J, Rojo F, Del Campo JM, Sauleda S, Anido J, Raspall G, Giralt J, Rosello J, Nicholson Rl, Mendelsohn J, Baselga J (2001) Activated extracellular signal-regulated kinases: Association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments. Cancer Research 61:6500-6510
90. Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124:471-484
91. Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE (1988) Normal Keratiniza-tion in A Spontaneously Immortalized Aneuploid Human Keratinocyte Cell-Line. Journal of Cell Biology 106:761-771
92. Boukamp P, Peter W, Pascheberg U, Altmeier S, Fasch-ing C, Stanbridge EJ, Fusenig NE (1995) Step-wise progression in human skin carcinogenesis in vitro involves mutational inactivation of p53, rasH oncogene activation and additional chromosome loss. Oncogene 11:961-969
93. Fusenig NE, Boukamp P (1998) Multiple stages and genetic alterations in immortalization, malignant transformation, and tumor progression of human skin keratinocytes. Molecular Carcinogenesis 23:144-158
94. Qin JZ, Chaturvedi V, Denning MF, Choubey D, Diaz MO, Nickoloff BJ (1999) Role of NF-kappaB in the apoptotic-resistant phenotype of keratinocytes. Journal of Biological Chemistry 274:37957-37964
95. Thorn T, Gniadecki R, Petersen AB, Vicanova J, Wulf HC (2001) Differences in activation of G2/M checkpoint in keratinocytes after genotoxic stress induced by hydrogen peroxide and ultraviolet A radiation. Free Radical Research 35:405-416
96. Boukamp P, Popp S, Altmeyer S, Hulsen A, Fasching C, Cremer T, Fusenig NE (1997) Sustained nontumorigen-ic phenotype correlates with a largely stable chromosome content during long-term culture of the human keratinocyte line HaCaT. Genes Chromosomes & Cancer 19:201-214
97. Leverkus M, Yaar M, Eller MS, Tang EH, Gilchrest BA (1998) Post-transcriptional regulation of UV induced TNF-alpha expression. Journal of Investigative Dermatology 110:353-357
98. Cohen EE, Lingen MW, Zhu B, Zhu H, Straza MW, Pierce C, Martin LE, Rosner MR (2006) Protein kinase C zeta mediates epidermal growth factor-induced growth of head and neck tumor cells by regulating mi-togen-activated protein kinase. Cancer Research 66:6296-6303
99. Babbar N, Casero RA (2006) Tumor necrosis factor-alpha increases reactive oxygen species by inducing spermine oxidase in human lung epithelial cells: A potential mechanism for inflammation-induced carcinogenesis. Cancer Research 66:11125-11130
100. Smedby KE, Baecklund E, Askling J (2006) Malignant lymphomas in autoimmunity and inflammation: A review of risks, risk factors, and lymphoma characteristics. Cancer Epidemiology Biomarkers & Prevention 15:2069-2077
101. Geborek P, Bladstrom A, Turesson C, Gulfe A, Peters-son IF, Saxne T, Olsson H, Jacobsson LTH (2005) Tumor necrosis factor blockers do not increase overall tumor risk in patients with rheumatoid arthritis, but may be associated with an increased risk of lymphomas. Annals of the Rheumatic Diseases 64:699-703
102. Askling J, Fored CM, Brandt L, Baecklund E, Bertilsson L, Feltelus N, Coster L, Geborek P, Jacobsson LT, Lindblad S, Lysholm J, Rantapaa-Dahlqvist S, Saxne T, Klareskog L (2005) Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumor necrosis factor antagonists. Annals of the Rheumatic Diseases 64:1421-1426
103. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matte-son EL, Montori V (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies - Systematic review and metaanalysis of rare harmful effects in randomized con-trolled trials. Jama-Journal of the American Medical Association 295:2275-2285