Molecular and Cellular Biochemistry

, Volume 289, Issue 1–2, pp 73–82 | Cite as

NFAT3 is Required for EGF-Induced COX-2 Transcription, but Neither iNOS Transcription Nor Cell Transformation in Cl 41 Cells

  • Jingxia Li
  • Haitian Lu
  • Chuanshu Huang


Epidermal growth factor (EGF) has been reported to act as a tumor promoter in several tissues, such as skin, in association with the induction of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). However, molecular mechanisms involved in these regulations are not well defined. This study addressed a potential role of nuclear factor of activated T cells 3 (NFAT3) in EGF-induced COX-2 and iNOS transcription and cell transformation in mouse epidermal Cl 41 cells. We found that EGF markedly induced anchorage-independent growth (cell transformation) of Cl 41 cells, as well as COX-2 (> 6-fold) and iNOS (> 5-fold) promoter-dependent transcription. The EGF-induced COX-2 transcription was blocked by knockdown of NFAT3 with NFAT3 siRNA, whereas the transcription of iNOS and cell transformation induced by EGF were not affected. Although our recent studies supported that NFAT3 plays an essential role in chemical carcinogen benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE)-induced cell transformation, the data presented here demonstrated that NFAT3 is required for EGF-induced COX-2 transcription, but neither iNOS transcription nor cell transformation, indicating that the role of NFAT3 in regulating cell transformation is carcinogen-specific.


EGF COX-2 NFAT3 siRNA cell transformation 



epidermal growth factor




inducible nitric oxide synthase


nuclear factor of activated T cells


nitric oxide


epidermal growth factor receptor




tumor necrosis factor alpha


Minimal Essential Medium


fetal bovine serum




activator protein-1




Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Casaco A, Diaz Y, Ledon N, Merino N, Vades O, Garcia G, Garcia B, Gonzalez G, Perez R: Effect of an EGF-cancer vaccine on wound healing and inflammatory models. J Surg Res 122(1): 130–134, 2004CrossRefPubMedGoogle Scholar
  2. 2.
    Sato T, Nakajima H, Fujio K, Mori Y: Ehancement of prostaglandin E2 production by epidermal growth factor requires the coordinate activation of cytosolic phospholipase A2 and cyclooxygenase 2 in human squamous carcinoma A431 cells. Prostaglandins 53: 355–369, 1997CrossRefPubMedGoogle Scholar
  3. 3.
    Carpenter G: Receptors for epidermal growth factor and other polypeptide mitogens. Annu Rev Biochem 56: 881–914, 1987CrossRefPubMedGoogle Scholar
  4. 4.
    Yoon JH, Gwak GY, Lee HY, Bronk SF, Werneberg NW, Gores GJ: Enhanced epidermal growth factor receptor activation in human cholangiocarcinoma cells. J Hepatol 41: 808–814, 2004CrossRefPubMedMATHGoogle Scholar
  5. 5.
    Maurizi M, Almadori G, Ferrandina G, Distefano M, Romanini ME, Cadoni G, Benedetti-Panici P, Paludetti G, Scambia G, Mancuso S: Prognostic significance of epidermal growth factor receptor in laryngeal squamous cell carcinoma. Br J Cancer 74: 1253–1257, 1996PubMedGoogle Scholar
  6. 6.
    Grandis JR, Melhem MF, Gooding WE, Day R, Holst VA, Wagener MM, Drenning SD, Tweardy DJ: Levels of TGF-α and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst 90: 824–832, 1998CrossRefPubMedGoogle Scholar
  7. 7.
    Lu Z, Ghosh S, Wang Z, Hunter T: Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of β-catenin, and enhanced tumor cell invasion. Cancer Cell 4: 499–515, 2003CrossRefPubMedGoogle Scholar
  8. 8.
    Kopp R, Rothbauer E, Ruge M, Arnholdt H, Spranger J, Muders M, Pfeiffer DG, Schildberg FW, Pfeiffer A: Clinical implications of the EGF receptor/ligand system for tumor progression and survival in gastrointestinal carcinomas: evidence for new therapeutic options. Recent Results Cancer Res 162: 115–132, 2003PubMedGoogle Scholar
  9. 9.
    Maihle NJ, Baron AT, Barrette BA, Boardman CH, Christensen TA, Cora EM, Faupel-Badger JM, Greenwood T, Juneja SC, Lafky JM, Lee H, Reiter JL, Podratz KC: EGF/ErbB receptor family in ovarian cancer. Cancer Treat Res 107: 247–258, 2002PubMedGoogle Scholar
  10. 10.
    Xing C, Imagawa W: Altered MAP kinase (ERK1, 2) regulation in primary cultures of mammary tumor cells: elevated basal activity and sustained response to EGF. Carcinogenesis 20: 1201–1208, 1999CrossRefPubMedGoogle Scholar
  11. 11.
    Chen LC, Chen BK, Chang JM, Chang WC: Essential role of c-Jun induction and coactivator p300 in epidermal growth factor-induced gene expression of cyclooxygenase-2 in human epidermoid carcinoma A431 cells. Biochimica et Biophysica Acta 1683: 38–48, 2004PubMedGoogle Scholar
  12. 12.
    Li J, Ma C, Huang Y, Luo J, Huang C: Differential requirement of EGF receptor and its tyrosine kinase for AP-1 transactivation induced by EGF and TPA. Oncogene 22: 211–219, 2003CrossRefPubMedGoogle Scholar
  13. 13.
    Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR: TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 266: 12866–12872, 1991PubMedGoogle Scholar
  14. 14.
    Hamasaki Y, Kitzler J, Hardman R, Nettesheim P, Eling TE: Phorbol ester and epidermal growth factor enhance the expression of two inducible prostaglandin H synthase genes in rat tracheal epithelial cells. Arch Biochem Biophys 304: 226–234, 1993CrossRefPubMedGoogle Scholar
  15. 15.
    Hla TT, Bailey JM: Differential recovery of prostacyclin synthesis in cultured vascular endothelial vs. smooth muscle cells after inactivation of cyclooxygenase with aspirin. Prostaglandins Leukot Essent Fatty Acids 36: 175–184, 1989CrossRefPubMedGoogle Scholar
  16. 16.
    Pash JM, Bailey JM: Inhibition by corticosteroids of epidermal growth factor-induced recovery of cyclooxygenase after aspirin inactivation. FASEB J 2: 2613–2618, 1988PubMedGoogle Scholar
  17. 17.
    Sakamoto C, Matsuda K, Nakano O, Konda Y, Matozaki T, Nishisaki H, Kasuga M: EGF stimulates both cyclooxygenase activity and cell proliferation of cultured guinea pig gastric mucous cells. J Gastroenterol 29 (Suppl 7): 73–76, 1994Google Scholar
  18. 18.
    Coffey RJ, Hawkey CJ, Damstrup L, Graves-Deal R, Daniel VC, Dempsey PJ, Chinery R, Kirkland SC, Dubois RN, Jetton TL, Morrow JD: Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells. Proc Natl Acad Sci USA 94: 657–622, 1997CrossRefPubMedADSGoogle Scholar
  19. 19.
    Kulkarni S, Rader JS, Zhang F, Liapis H, Koki AT, Masferrer JL, Subbaramaiah K, Dannenberg AJ: Cyclooxygenase-2 is overexpressed in human cervical cancer. Clinic Cancer Res 7: 429–434, 2001Google Scholar
  20. 20.
    Jiang B, Xu S, Brecher P, Cohen RA: Growth factors enhance interleukin-1 β-induced persistent activation of nuclear factor-γB in rat vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 22: 1811–1816, 2002CrossRefPubMedGoogle Scholar
  21. 21.
    Gallo O, Fabbroni V, Sardi I, Magnelli L, Boddi V, Franchi A: Correlation between nitric oxide and cyclooxygenase-2 pathways in head and neck squamous cell carcinomas. Biochem Biophys Res Commun 299: 517–524, 2002CrossRefPubMedGoogle Scholar
  22. 22.
    Cianchi F, Cortesini C, Fantappié O, Messerini L, Sardi I, Lasagna N, Perna F, Fabbroni V, Di Felice A, Perigli G, Mazzanti R, Masini E: Cyclooxygenase-2 activation mediates the proangiogenic effect of nitric oxide in colorectal cancer. Clinic Cancer Res 10: 2694–2704, 2004CrossRefGoogle Scholar
  23. 23.
    Kitagawa K, Hamada Y, Kato Y, Nakai K, Nishizawa M, Ito S, Okumura T: Epidermal growth factor and interleukin-1 β synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 287: G1188–1193, 2004CrossRefPubMedGoogle Scholar
  24. 24.
    Tsujii M, Dubois RN: Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83: 493–501, 1995CrossRefPubMedGoogle Scholar
  25. 25.
    Tsujii M, Kawano S, Dubois RN: Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proc Natl Acad Sci USA 94: 3336–3340, 1997CrossRefPubMedADSGoogle Scholar
  26. 26.
    Liu XH, Kirschenbaum A, Yao S, Lee R, Holland JF, Levine AC: Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo. J Urol 164: 820–825, 2000CrossRefPubMedGoogle Scholar
  27. 27.
    Prescott SM, Fitzpatrick FA: Cyclooxygenase-2 and carcinogenesis. Biochim Biophys Acta 1470: M69–78, 2000PubMedGoogle Scholar
  28. 28.
    Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, Dubois RN: Upregulation of cyclooxygenase-2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 107: 1183–1188, 1994PubMedGoogle Scholar
  29. 29.
    Ristimaki A, Honkanen N, Jankala H, Sipponen P, Harkonen M: Expression of cyclooxygenase 2 in huamn gastric cancer. Cancer Res 57: 1276–1280, 1997PubMedGoogle Scholar
  30. 30.
    Hwang D, Scollard D, Byrne J, Levine E: Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst 90: 455–460, 1998CrossRefPubMedGoogle Scholar
  31. 31.
    Okami J, Yamamoto H, Fujiwara Y, Tsujie M, Kondo M, Noura S, Oshima S, Nagano H, Dono K, Umeshita K, Ishikawa O, Sakon M, Matsuura N, Nakamori S, Monden M: Overexpression of cyclooxygenase-2 in carcinoma of the pancreas. Clinical Cancer Res 5: 2018–2024, 1999Google Scholar
  32. 32.
    Hida T, Yatabe Y, Achiwa H, Muramatsu H, Kozaki K, Nakamura S, Ogawa M, Mitsudomi T, Sugiura T, Takahashi T: Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res 58: 3761–3764, 1998PubMedGoogle Scholar
  33. 33.
    Thun MJ, Henley SJ, Patrono C: Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 94: 252–266, 2002PubMedGoogle Scholar
  34. 34.
    Hofseth LJ, Hussain SP, Wogan GN, Harris CC: Nitric oxide in cancer and chemoprevention. Free Radic Biol Med 28: 1387–1404, 2000CrossRefPubMedGoogle Scholar
  35. 35.
    Rincon M, Flavell RA: Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells. Mol Cell Biol 17: 1522–1534, 1997PubMedGoogle Scholar
  36. 36.
    Durand DB, Shaw JP, Bush MR, Replogle RE, Belagaje R, Crabtree GR: Characterization of antigen receptor response elements within the interleukin-2 enhancer. Mol Cell Biol 8: 1715–1724, 1988PubMedGoogle Scholar
  37. 37.
    Serfling E, Barthelmas R, Pfeuffer I, Schenk B, Zarius S, Swoboda R, Mercurio F, Karin M: Ubiquitous and lymphocyte-specific factors are involved in the induction of the mouse interleukin 2 gene in T lymphocytes. EMBO J 8: 465–473, 1989PubMedGoogle Scholar
  38. 38.
    Shaw JP, Utz PJ, Durand DB, Toole JJ, Emmel EA, Crabtree GR: Identification of a putative regulator of early T cell activation genes. Science 241: 202–205, 1989ADSGoogle Scholar
  39. 39.
    Rao A, Luo C, Hogan PG: Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 15: 707–747, 1997CrossRefPubMedGoogle Scholar
  40. 40.
    Huang C, Mattjus P, Ma WY, Rincon M, Chen NY, Brown RE, Dong Z: Involvement of nuclear factor of activated T cells activation in UV response. Evidence from cell culture and transgenic mice. J Biol Chem 275: 9143–9149, 2000CrossRefPubMedGoogle Scholar
  41. 41.
    Chow CW, Rincon M, Cavanagh J, Dickens M, Davis RJ: Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway. Science 278: 1638–1642, 1997CrossRefPubMedADSGoogle Scholar
  42. 42.
    Iniguez MA, Martinez-Martinez S, Punzon C, Redondo JM, Fresno M: An essential role of the nuclear factor of activated T cells in the regulation of the expression of the cyclooxygenase-2 gene in human T lymphocytes. J Biol Chem 275: 23627–23635, 2000CrossRefPubMedGoogle Scholar
  43. 43.
    Jauliac S, Lopez-Rodriguez C, Shaw LM, Brown LF, Rao A, Toker A: The role of NFAT transcription factors in integrin-mediated carcinoma invasion. Nat Cell Biol 4: 540–544, 2002CrossRefPubMedGoogle Scholar
  44. 44.
    Huang C, Li J, Costa M, Zhang Z, Leonard SS, Castranova V, Vallythan V, Ju G, Shi X: Hydrogen Peroxide Mediates Activation of Nuclear Factor of Activated T Cells (NFAT) by Nickel Subsulfide. Cancer Res 61: 8051–8057, 2001PubMedGoogle Scholar
  45. 45.
    Huang C, Ding M, Li J, Leonard SS, Rojanasakul Y, Castranova V, Vallyathan V, Ju G, Shi X: Vanadium-induced nuclear factor of activated T cells through hydrogen peroxide. J Biol Chem 276: 22397–22403, 2001CrossRefPubMedGoogle Scholar
  46. 46.
    Subbaramaiah K, Cole PA, Dannenberg AJ: Retinoids and carnosol suppress cyclooxygenase-2 transcription by CREB-binding protein/p300-dependent and independent mechanisms. Cancer Res 62: 2522–2530, 2002PubMedGoogle Scholar
  47. 47.
    de Vera ME, Shapiro RA, Nussler AK, Mudgett JS, Simmons RL, Morris Jr SM, Billiar TR, Geller DA: Transcriptional regulation of human inducible nitric oxide synthase (NOS2) gene by cytokines: initial analysis of the human NOS2 promoter. Proc Natl Acad Sci USA 93: 1054–1059, 1996CrossRefPubMedADSGoogle Scholar
  48. 48.
    Huang C, Li J, Ma WY, Dong Z: JNK activation is required for JB6 cell transformation induced by tumor necrosis factor-alpha but not by 12-O-tetradecanoylphorbol-13-acetate. J Biol Chem 274: 29672–29676, 1999CrossRefPubMedGoogle Scholar
  49. 49.
    de Gregorio R, Iniguez MA, Fresno M, Alemany S: Cot kinase induces cyclooxygenase-2 expression in T cells through activation of nuclear factor of activated T cells. J Biol Chem 276: 27003–27009, 2001CrossRefPubMedGoogle Scholar
  50. 50.
    Hogan PG, Chen L, Nardone J, Rao A: Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev 17: 2205–2232, 2003PubMedCrossRefGoogle Scholar
  51. 51.
    Huh YH, Kim SH, Kim SJ, Chun JS: Differential status-dependent regulation of cyclooxygenase-2 expression and prostaglandin E2 production by epidermal growth factor via mitogen-activated protein kinase in articular chondrocytes. J Biol Chem 278: 9691–9697, 2003CrossRefPubMedGoogle Scholar
  52. 52.
    Zhao H, Tian W, Tai C, Cohen DM: Hypertonic induction of COX-2 expression in renal medullary epithelial cells requires transactivation of the EGFR. Am J Physiol Renal Physiol 285: F281–F288, 2003PubMedGoogle Scholar
  53. 53.
    Ashida M, Bito T, Budiyanto A, Ichihashi M, Ueda M: Involvement of EGF receptor activation in the induction of cyclooxygenase-2 in HaCaT keratinocytes after UVB. Exp Dermatol 12: 445–452, 2003CrossRefPubMedGoogle Scholar
  54. 54.
    Pawliczak R, Logun C, Madara P, Lawrence M, Woszczek G, Ptasinska A, Kowalski ML, Wu T, Shelhamer JH: Cytosolic phospholipase A2 Group IVα but not secreted phospholipase A2 Group IIA, V, or X induces interleukin-8 and cyclooxygenase-2 gene and protein expression through peroxisome proliferator-activated receptors γ1 and 2 in human lung cells. J Biol Chem 279: 48550–48561, 2004CrossRefPubMedGoogle Scholar
  55. 55.
    Starke GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD: How cells respond to interferons. Annu Rev Biochem 67: 227–264, 1998CrossRefPubMedGoogle Scholar
  56. 56.
    Zhang Z, Sheng H, Shao J, Beauchamp RD, Dubois RN: Posttranscriptional regulation of cyclooxygenase-2 in rat intestinal epithelial cells. Neoplasia 2: 523–530, 2000CrossRefPubMedGoogle Scholar
  57. 57.
    Sheng H, Shao J, Dubois RN: K-Ras-mediated increase in cyclooxygenase 2 mRNA stability involves activation of the protein kinase B1. Cancer Res 61: 2670–2675, 2001PubMedGoogle Scholar
  58. 58.
    Nathan C, Xie QW: Nitric oxide synthase: Roles, tolls, and controls. Cell 78: 915–918, 1994CrossRefPubMedGoogle Scholar
  59. 59.
    Marletta MA: Nitric oxide synthase structure and mechanism. J Biol Chem 268: 12231–12234, 1993PubMedGoogle Scholar
  60. 60.
    Sugimoto T, Haneda M, Sawano H, Isshiki K, Maeda S, Koya D, Inoki K, Yasuda H, Kashiwagi A, Kikkawa R: Endothelin-1 induces cyclooxygenase-2 expression via nuclear factor of activated T-cell transcription factor in glomerular mesangial cells. J Am Soc Nephrol 12: 1359–1368, 2001PubMedGoogle Scholar
  61. 61.
    Neal JW, Clipstone NA: A constitutively active NFATCl mutant induces a transformed phenotype in 3T3-L1 fibroblasts. J Biol Chem 278: 17246–17254, 2003CrossRefPubMedGoogle Scholar
  62. 62.
    Huang C, Ma WY, Dong Z: Requirement for phosphatidylinositol 3-kinase in epidermal growth factor-induced AP-1 transactivation and transformation in JB6 P+ cells. Mol Cell Biol 16: 6427–6435, 1996PubMedGoogle Scholar
  63. 63.
    Singletary SE, Baker FL, Spitzer G, Tucker SL, Tomasovic B, Brock WA, Ajani JA, Kelly AM: Biological effect of epidermal growth factor on the in vitro growth of human tumors. Cancer Res 47: 403–406, 1987PubMedGoogle Scholar
  64. 64.
    Shima I, Sasaguri Y, Kusukawa J, Nakano R, Yamana H, Fujita H, Kakegawa T, Morimatsu M: Production of matrix metalloproteinase 9 (92-kDa gelatinase) by human oseophageal squamous cell carcinoma in response to epidermal growth factor. Br J Cancer 67: 721–727, 1993PubMedGoogle Scholar
  65. 65.
    Rao CV: Nitric oxide signaling in colon cancer chemoprevention. Mutat Res 555: 107–119, 2004PubMedADSGoogle Scholar
  66. 66.
    Gullick WJ, Srinivasan R: The type 1 growth factor family: new ligands and receptors and their role in breast cancer. Breast Cancer Res Treat 52: 43–53, 1998CrossRefPubMedGoogle Scholar
  67. 67.
    Yarden Y: The EGFR family and its ligands in human cancer: signaling mechanisms and therapeutic opportunities. Eur J Cancer 37: S3–S8, 2001CrossRefPubMedGoogle Scholar
  68. 68.
    Wells A: EGF receptor. Int J Biochem Cell Biol 31: 637–643, 1999CrossRefPubMedGoogle Scholar
  69. 69.
    Wu W, Silbajoris RA, Whang YE, Graves LM, Bromberg PA, Samet JM: p38 and EGF receptor kinase-mediated activation of the phosphatidylinositol 3-kinase/Akt pathway is required for Zn2+-induced cyclooxygenase-2 expression. Am J Physiol Lung Cell Mol Physiol 289(5): L883–9, 2005CrossRefPubMedGoogle Scholar
  70. 70.
    Chang MS, Chen BC, Yu MT, Sheu JR, Chen TF, Lin CH: Phorbol 12-myristate 13-acetate upregulates cyclooxygenase-2 expression in human pulmonary epithelial cells via Ras, Raf-1, ERK, and NF-kappaB, but not p38 MAPK, pathways. Cell Signal 17(3): 299–310, 2005CrossRefPubMedGoogle Scholar
  71. 71.
    Guo YS, Hellmich MR, Wen XD, Townsend Jr. CM: Activator Protein-1 Transcription Factor Mediates Bombesin-stimulated Cyclooxygenase-2 Expression in Intestinal Epithelial Cells. J Biol Chem 276(25): 22941–22947, 2001CrossRefPubMedGoogle Scholar
  72. 72.
    Subbaramaiah K, Norton L, Gerald W, Dannenberg AJ: Cyclo-oxygenase-2 Is Overexpressed in HER-2/neu-positive Breast Cancer. J Biol Chem 277(21): 18649–18657, 2002CrossRefPubMedGoogle Scholar
  73. 73.
    Yamaguchi K, Lantowski A, Dannenberg AJ, Subbaramaiah K: Histone deacetylase inhibitors suppress the induction of c-Jun and its target genes including COX-2. J Biol Chem 280(38): 32569–32577, 2005CrossRefPubMedGoogle Scholar
  74. 74.
    Chun KS, Kim SH, Song YS, Surh YJ: Celecoxib inhibits phorbol ester-induced expression of COX-2 and activation of AP-1 and p38 MAP kinase in mouse skin. Carcinogenesis 25(5): 713–722, 2004CrossRefPubMedGoogle Scholar
  75. 75.
    Gallo O, Fabbroni V, Sardi I, Magnelli L, Boddi V, Franchi A: Correlation between nitric oxide and cyclooxygenase-2 pathways in head and neck squamous cell carcinomas. Biochem Biophys Res Commun 299(4): 517–524, 2002CrossRefPubMedGoogle Scholar
  76. 76.
    Kitagawa K, Hamada Y, Kato Y, Nakai K, Nishizawa M, Ito S, Okumura T: Epidermal growth factor and interleukin-1 beta synergistically stimulate the production of nitric oxide in rat intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 287(6): G1188–1193, 2004CrossRefPubMedGoogle Scholar
  77. 77.
    Banan A, Zhang LJ, Shaikh M, Fields JZ, Farhadi A, Keshavarzian A: Key role of PLC-gamma in EGF protection of epithelial barrier against iNOS upregulation and F-actin nitration and disassembly. Am J Physiol Cell Physiol 285(4): C977–993, 2003PubMedGoogle Scholar
  78. 78.
    Crabtree GR, Clipstone NA: Signal transmission between the plasma membrane and nucleus of T lymphocytes. Annu Rev Biochem 63: 1045–1083, 1994CrossRefPubMedGoogle Scholar
  79. 79.
    Chen L, Glover JN, Hogan PG, Rao A, Harrison SC: Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA. Nature 392: 42–48, 1998CrossRefPubMedADSGoogle Scholar
  80. 80.
    Jiang H, Yamamoto S, Nishikawa K, Kato R: Anti-tumor-promoting action of FK506, a potent immunosuppressive agent. Carcinogenesis 14: 67–71, 1993PubMedGoogle Scholar
  81. 81.
    Singh RK, Gutman M, Reich R, Bar-Eli M: Ultraviolet B irradiation promotes tumorigenic and metastatic properties in primary cutaneous melanoma via induction of interleukin 8. Cancer Res 55: 3669–3674, 1995PubMedGoogle Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  1. 1.Nelson Institute of Environmental MedicineNew York University School of MedicineTuxedoUSA

Personalised recommendations