Skip to main content
SpringerLink
Log in

Targeting UVB Mediated Signal Transduction Pathways for the Chemoprevention of Squamous Cell Carcinoma

  • Chapter
  • First Online:
Signaling Pathways in Squamous Cancer

  • 575 Accesses

Abstract

The high incidence of skin cancer in the USA is directly related to solar radiation exposure. There is also a disturbing increase in the incidence of both nonmelanoma and melanoma skin cancers in the USA. There is evidence that the use of sunblocks or sunscreens is not totally effective in preventing skin cancer. Therefore, there is a need for new mechanism-based approaches to prevent solar radiation-induced skin cancers. Ultraviolet (UV) light can initiate skin tumor development through DNA damage and critical mutations, for instance in the p53 tumor suppressor gene. UV light can also promote the clonal expansion of these initiated cells through signal transduction pathways to give rise to benign tumors. Some of these signaling pathways mediate the downstream activation of the transcription factor complex, activator protein 1, which has been shown to play a functional role in UV induced skin carcinogenesis. Targeting of these signaling pathways using natural products and small molecule inhibitors is being explored for early chemoprevention of nonmelanoma skin cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Affara NI, Trempus CS et al (2006) Activation of Akt and mTOR in CD34+/K15+ keratinocyte stem cells and skin tumors during multi-stage mouse skin carcinogenesis. Anticancer Res 26(4B):2805–2820

    PubMed  CAS  Google Scholar 

  • Agarwal R, Katiyar SK et al (1993) Protection against ultraviolet B radiation-induced effects in the skin of SKH-1 hairless mice by a polyphenolic fraction isolated from green tea. Photochem Photobiol 58(5):695–700

    Article  PubMed  CAS  Google Scholar 

  • Alberts DS, Dorr RT et al (2000) Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine. Cancer Epidemiol Biomarkers Prev 9(12):1281–1286

    PubMed  CAS  Google Scholar 

  • Alberts D, Ranger-Moore J et al (2004) Safety and efficacy of dose-intensive oral vitamin A in subjects with sun-damaged skin. Clin Cancer Res 10(6):1875–1880

    Article  PubMed  CAS  Google Scholar 

  • An KP, Athar M et al (2002) Cyclooxygenase-2 expression in murine and human nonmelanoma skin cancers: implications for therapeutic approaches. Photochem Photobiol 76(1):73–80

    Article  PubMed  CAS  Google Scholar 

  • Ananthaswamy HN, Pierceall WE (1990) Molecular mechanisms of ultraviolet radiation carcinogenesis. Photochem Photobiol 52(6):1119–1136

    Article  PubMed  CAS  Google Scholar 

  • Angel P (1995) The role and regulation of the Jun proteins in response to phorbol esters and UV light. In: Baeuerle PA (ed) Inducible gene expression. Birkhouser, Boston

    Google Scholar 

  • Assefa Z, Garmyn M et al (1997) Differential stimulation of ERK and JNK activities by ultraviolet B irradiation and epidermal growth factor in human keratinocytes. J Invest Dermatol 108(6):886–891

    Article  PubMed  CAS  Google Scholar 

  • Baade PD, Balanda KP et al (1996) Changes in skin protection behaviors, attitudes, and sunburn: in a population with the highest incidence of skin cancer in the world. Cancer Detect Prev 20(6):566–575

    PubMed  CAS  Google Scholar 

  • Bachelor MA, Cooper SJ et al (2005) Inhibition of p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase decreases UVB-induced activator protein-1 and ­cyclooxygenase-2 in a SKH-1 hairless mouse model. Mol Cancer Res 3(2):90–99

    Article  PubMed  CAS  Google Scholar 

  • Bair WB 3rd, Hart N et al (2002) Inhibitory effects of sodium salicylate and acetylsalicylic acid on UVB-induced mouse skin carcinogenesis. Cancer Epidemiol Biomarkers Prev 11(12):1645–1652

    PubMed  CAS  Google Scholar 

  • Barthelman M, Bair WB 3rd et al (1998a) (-)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity. Carcinogenesis 19(12):2201–2204

    Article  PubMed  CAS  Google Scholar 

  • Barthelman M, Chen W et al (1998b) Inhibitory effects of perillyl alcohol on UVB-induced murine skin cancer and AP-1 transactivation. Cancer Res 58(4):711–716

    PubMed  CAS  Google Scholar 

  • Baur JA, Pearson KJ et al (2006) Resveratrol improves health and survival of mice on a ­high-calorie diet. Nature 444(7117):337–342

    Article  PubMed  CAS  Google Scholar 

  • Bender K, Blattner C et al (1997) UV-induced signal transduction. J Photochem Photobiol B 37(1–2):1–17

    Article  PubMed  CAS  Google Scholar 

  • Bennett A, Carroll MA et al (1982) Prostaglandins and human lung carcinomas. Br J Cancer 46(6):888–893

    PubMed  CAS  Google Scholar 

  • Bernstein LR, Colburn NH (1989) AP1/jun function is differentially induced in promotion-sensitive and resistant JB6 cells. Science 244(4904):566–569

    Article  PubMed  CAS  Google Scholar 

  • Birkenfeld S, Zaltsman YA et al (1987) Antitumor effects of inhibitors of arachidonic acid cascade on experimentally induced intestinal tumors. Dis Colon Rectum 30(1):43–46

    Article  PubMed  CAS  Google Scholar 

  • Birt DF, Przybyszewski J et al (2004) Identification of molecular targets for dietary energy ­restriction prevention of skin carcinogenesis: an idea cultivated by Edward Bresnick. J Cell Biochem 91(2):258–264

    Article  PubMed  CAS  Google Scholar 

  • Black HS, Herd JA et al (1994) Effect of a low-fat diet on the incidence of actinic keratosis. N Engl J Med 330(18):1272–1275

    Article  PubMed  CAS  Google Scholar 

  • Bode AM, Dong Z (2003) Mitogen-activated protein kinase activation in UV-induced signal ­transduction. Sci STKE 2003(167):RE2

    Article  PubMed  Google Scholar 

  • Boutwell RK (1974) The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol 2(4):419–443

    Article  PubMed  CAS  Google Scholar 

  • Bowker SL, Majumdar SR et al (2006) Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diab Care 29(2):254–258

    Article  Google Scholar 

  • Brash DE, Rudolph JA et al (1991) A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci USA 88(22):10124–8

    Article  PubMed  CAS  Google Scholar 

  • Buckman SY, Gresham A et al (1998) COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer. Carcinogenesis 19(5):723–729

    Article  PubMed  CAS  Google Scholar 

  • Buzzai M, Jones RG et al (2007) Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res 67(14):6745–6752

    Article  PubMed  CAS  Google Scholar 

  • Campbell C, Quinn AG et al (1993) p53 mutations are common and early events that precede tumor invasion in squamous cell neoplasia of the skin. J Invest Dermatol 100(6):746–748

    Article  PubMed  CAS  Google Scholar 

  • Carpenter CL, Duckworth BC et al (1990) Purification and characterization of phosphoinositide 3-kinase from rat liver. J Biol Chem 265(32):19704–19711

    PubMed  CAS  Google Scholar 

  • Chen W, Bowden GT (1999) Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes. Oncogene 18(52):7469–7476

    Article  PubMed  CAS  Google Scholar 

  • Chen W, Bowden GT (2000) Role of p38 mitogen-activated protein kinases in ultraviolet-B ­irradiation-induced activator protein 1 activation in human keratinocytes. Mol Carcinog 28(4):196–202

    Article  PubMed  CAS  Google Scholar 

  • Chen W, Borchers AH et al (1998) UVB irradiation-induced activator protein-1 activation correlates with increased c-fos gene expression in a human keratinocyte cell line. J Biol Chem 273(48):32176–32181

    Article  PubMed  CAS  Google Scholar 

  • Chen W, Dong Z et al (1999) Inhibition of ultraviolet B–induced c-fos gene expression and p38 mitogen-activated protein kinase activation by (-)-epigallocatechin gallate in a human keratinocyte cell line. Mol Carcinog 24(2):79–84

    Article  PubMed  CAS  Google Scholar 

  • Chen W, Tang Q et al (2001) Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes. Oncogene 20(29):3921–3926

    Article  PubMed  CAS  Google Scholar 

  • Chen SJ, Nakahara T et al (2009) Activation of the mammalian target of rapamycin signalling pathway in epidermal tumours and its correlation with cyclin-dependent kinase 2. Br J Dermatol 160(2):442–445

    Article  PubMed  Google Scholar 

  • Conney AH, Wang ZY et al (1992) Inhibitory effect of green tea on tumorigenesis by chemicals and ultraviolet light. Prev Med 21(3):361–369

    Article  PubMed  CAS  Google Scholar 

  • Cooper SJ, MacGowan J et al (2003) Expression of dominant negative c-jun inhibits ultraviolet B-induced squamous cell carcinoma number and size in an SKH-1 hairless mouse model. Mol Cancer Res 1(11):848–854

    PubMed  CAS  Google Scholar 

  • Corradetti MN, Inoki K et al (2004) Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev 18(13):1533–1538

    Article  PubMed  CAS  Google Scholar 

  • Coso OA, Chiariello M et al (1995) Transforming G protein-coupled receptors potently activate JNK (SAPK) Evidence for a divergence from the tyrosine kinase signaling pathway. J Biol Chem 270(10):5620–5624

    Article  PubMed  CAS  Google Scholar 

  • Danpure HJ, Tyrrell RM (1976) Oxygen-dependence of near UV (365 NM) lethality and the interaction of near UV and X-rays in two mammalian cell lines. Photochem Photobiol 23(3):171–177

    Article  PubMed  CAS  Google Scholar 

  • De Leo VA, Horlick H et al (1984) Ultraviolet radiation induces changes in membrane metabolism of human keratinocytes in culture. J Invest Dermatol 83(5):323–326

    Article  PubMed  Google Scholar 

  • Domann FE, Levy JP et al (1994) Stable expression of a c-JUN deletion mutant in two malignant mouse epidermal cell lines blocks tumor formation in nude mice. Cell Growth Differ 5(1):9–16

    PubMed  CAS  Google Scholar 

  • Dong Z, Ma W et al (1997) Inhibition of tumor promoter-induced activator protein 1 activation and cell transformation by tea polyphenols, (-)-epigallocatechin gallate, and theaflavins. Cancer Res 57(19):4414–4419

    PubMed  CAS  Google Scholar 

  • Dorr RT, Ertl G et al (2004) Effects of a superpotent melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers. Arch Dermatol 140(7):827–835

    Article  PubMed  CAS  Google Scholar 

  • Dvorakova K, Dorr RT et al (1999) Pharmacokinetics of the green tea derivative, EGCG, by the topical route of administration in mouse and human skin. Cancer Chemother Pharmacol 43(4):331–335

    Article  PubMed  CAS  Google Scholar 

  • Einspahr JG, Stratton SP et al (2002) Chemoprevention of human skin cancer. Crit Rev Oncol Hematol 41(3):269–285

    Article  PubMed  Google Scholar 

  • Einspahr JG, Bowden GT et al (2003) Skin cancer chemoprevention: strategies to save our skin. Recent Results Cancer Res 163:151–64, discussion 264-266

    PubMed  CAS  Google Scholar 

  • Einspahr JG, Bowden GT et al (2008) Cross-validation of Murine UV Signal Transduction Pathways in Human Skin. Photochem Photobiol 84(2):463–476

    Article  PubMed  CAS  Google Scholar 

  • Elmets CA (1992) Cutaneous photocarcinogenesis. In: Mukhtar H (ed) Pharmacology of the skin. CRC, Boca Raton

    Google Scholar 

  • Euvrard S, Ulrich C et al (2004) Immunosuppressants and skin cancer in transplant patients: focus on rapamycin. Dermatol Surg 30(4 Pt 2):628–633

    Article  PubMed  Google Scholar 

  • Evans JM, Donnelly LA et al (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330(7503):1304–1305

    Article  PubMed  Google Scholar 

  • Faivre S, Kroemer G et al (2006) Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov 5(8):671–688

    Article  PubMed  CAS  Google Scholar 

  • Fay JR, Steele V et al (2009) Energy homeostasis and cancer prevention: the AMP-activated protein kinase. Cancer Prev Res (Phila Pa) 2(4):301–309

    CAS  Google Scholar 

  • Finch JS, Bowden GT (1996) PCR/RFLP assay for copy number of mutant and wild-type alleles. Biotechniques 21(6):1055–1060

    PubMed  CAS  Google Scholar 

  • Findlay GM (1928) Ultraviolet light and skin cancer. Lancet 2:1070–1075

    Article  Google Scholar 

  • Fischer SM, Lo HH et al (1999) Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. Mol Carcinog 25(4):231–240

    Article  PubMed  CAS  Google Scholar 

  • Fisher GJ, Talwar HS et al (1998) Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo. J Clin Invest 101(6):1432–1440

    Article  PubMed  CAS  Google Scholar 

  • Fry RJ, Ley RD (1989) Ultraviolet radiation-induced skin cancer. In: Conti CJ, Slaga TJ, Klein-Szanto JP (eds) Skin tumors: experimental and clinical aspects. Raven, New York

    Google Scholar 

  • Fry DW, Kraker AJ et al (1994) A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science 265(5175):1093–1095

    Article  PubMed  CAS  Google Scholar 

  • Gensler HL, Aickin M et al (1990) Cumulative reduction of primary skin tumor growth in UV-irradiated mice by the combination of retinyl palmitate and canthaxanthin. Cancer Lett 53(1):27–31

    Article  PubMed  CAS  Google Scholar 

  • Gensler HL, Timmermann BN et al (1996) Prevention of photocarcinogenesis by topical administration of pure epigallocatechin gallate isolated from green tea. Nutr Cancer 26(3):325–335

    Article  PubMed  CAS  Google Scholar 

  • Glasgow WC, Afshari CA et al (1992) Modulation of the epidermal growth factor mitogenic response by metabolites of linoleic and arachidonic acid in Syrian hamster embryo fibroblasts. Differential effects in tumor suppressor gene (+) and (-) phenotypes. J Biol Chem 267(15):10771–10779, ST

    PubMed  CAS  Google Scholar 

  • Gonzales M, Bowden GT (2002a) Nordihydroguaiaretic acid-mediated inhibition of ultraviolet B-induced activator protein-1 activation in human keratinocytes. Mol Carcinog 34(2):102–111

    Article  PubMed  CAS  Google Scholar 

  • Gonzales M, Bowden GT (2002b) The role of PI 3-kinase in the UVB-induced expression of c-fos. Oncogene 21(17):2721–2728

    Article  PubMed  CAS  Google Scholar 

  • Gonzales M, Bowden GT (2002c) Ultraviolet B (UVB) induction of the c-fos promoter is mediated by phospho-cAMP response element binding protein (CREB) binding to CRE and c-fos activator protein 1 site (FAP1) cis elements. Gene 293(1–2):169–179

    Article  PubMed  CAS  Google Scholar 

  • Goodman GE, Alberts DS et al (1983) Phase I trial of retinol in cancer patients. J Clin Oncol 1(6):394–399

    PubMed  CAS  Google Scholar 

  • Gresham A, Masferrer J et al (1996) Increased synthesis of high-molecular-weight cPLA2 mediates early UV-induced PGE2 in human skin. Am J Physiol 270(4 Pt 1):C1037–1050

    PubMed  CAS  Google Scholar 

  • Grewe M, Trefzer U et al (1993) Analysis of the mechanism of ultraviolet (UV) B radiation-induced prostaglandin E2 synthesis by human epidermoid carcinoma cells. J Invest Dermatol 101(4):528–531

    Article  PubMed  CAS  Google Scholar 

  • Han S, Roman J (2006) Rosiglitazone suppresses human lung carcinoma cell growth through PPARgamma-dependent and PPARgamma-independent signal pathways. Mol Cancer Ther 5(2):430–437

    Article  PubMed  CAS  Google Scholar 

  • Hanson D, Bodian A et al (1989) Ultraviolet-A (320-400nm) induces phospholipase activation in human keratinocytes in culture. Clin Res 37:731A

    Google Scholar 

  • He G, Sung YM et al (2006) Thiazolidinediones inhibit insulin-like growth factor-i-induced activation of p70S6 kinase and suppress insulin-like growth factor-I tumor-promoting activity. Cancer Res 66(3):1873–1878

    Article  PubMed  CAS  Google Scholar 

  • Herrlich KM (1989) Cis-and trans-acting genetic elements responsible for induction of specific genes by tumor promoters, serum factors, and stress. In: Colburn N (ed) Genes and signal transduction in multistage carcinogenesis. Marcel Dekker, New York/Basel

    Google Scholar 

  • Herrlich P, Ponta H et al (1992) DNA damage-induced gene expression: signal transduction and relation to growth factor signaling. Rev Physiol Biochem Pharmacol 119:187–223

    PubMed  CAS  Google Scholar 

  • Higashi Y, Kanekura T et al (2000) Enhanced expression of cyclooxygenase (COX)-2 in human skin epidermal cancer cells: evidence for growth suppression by inhibiting COX-2 expression. Int J Cancer 86(5):667–671

    Article  PubMed  CAS  Google Scholar 

  • Holbrook NJ, Fornace AJ Jr (1991) Response to adversity: molecular control of gene activation following genotoxic stress. New Biol 3(9):825–833

    PubMed  CAS  Google Scholar 

  • Hsu TC, Young MR et al (2000) Activator protein 1 (AP-1)- and nuclear factor kappaB (NF-kappaB)-dependent transcriptional events in carcinogenesis. Free Radic Biol Med 28(9):1338–1348

    Article  PubMed  CAS  Google Scholar 

  • Huang MT, Wang ZY et al (1992) Inhibitory effects of curcumin on tumor initiation by benzo[a]pyrene and 7, 12-dimethylbenz[a]anthracene. Carcinogenesis 13(11):2183–2186

    Article  PubMed  CAS  Google Scholar 

  • Huang C, Ma W et al (1996) Ultraviolet B-induced activated protein-1 activation does not require epidermal growth factor receptor but is blocked by a dominant negative PKClambda/iota. J Biol Chem 271(49):31262–31268

    Article  PubMed  CAS  Google Scholar 

  • Iordanov M, Bender K et al (1997) CREB is activated by UVC through a p38/HOG-1-dependent protein kinase. EMBO J 16(5):1009–1022

    Article  PubMed  CAS  Google Scholar 

  • Jacobson EL, Kim H et al (2007) A topical lipophilic niacin derivative increases NAD, epidermal differentiation and barrier function in photodamaged skin. Exp Dermatol 16(6):490–499

    Article  PubMed  CAS  Google Scholar 

  • Johnson TM, Dolan OM et al (1998) Clinical and histologic trends of melanoma. J Am Acad Dermatol 38(5 Pt 1):681–686

    Article  PubMed  CAS  Google Scholar 

  • Kabuyama Y, Hamaya M et al (1998) Wavelength specific activation of PI 3-kinase by UVB irradiation. FEBS Lett 441(2):297–301

    Article  PubMed  CAS  Google Scholar 

  • Kang-Rotondo CH, Miller CC et al (1993) Enhanced keratinocyte prostaglandin synthesis after UV injury is due to increased phospholipase activity. Am J Physiol 264(2 Pt 1):C396–C401

    PubMed  CAS  Google Scholar 

  • Kanjilal S, Pierceall WE et al (1993) High frequency of p53 mutations in ultraviolet ­radiation-induced murine skin tumors: evidence for strand bias and tumor heterogeneity. Cancer Res 53(13):2961–2964

    PubMed  CAS  Google Scholar 

  • Kanjilal S, Strom SS et al (1995) p53 mutations in nonmelanoma skin cancer of the head and neck: molecular evidence for field cancerization. Cancer Res 55(16):3604–3609

    PubMed  CAS  Google Scholar 

  • Katiyar SK, Elmets CA et al (1995a) Protection against ultraviolet-B radiation-induced local and systemic suppression of contact hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols. Photochem Photobiol 62(5):855–861

    Article  PubMed  CAS  Google Scholar 

  • Katiyar SK, Rupp CO et al (1995b) Inhibition of 12-O-tetradecanoylphorbol-13-acetate and other skin tumor-promoter-caused induction of epidermal interleukin-1 alpha mRNA and protein expression in SENCAR mice by green tea polyphenols. J Invest Dermatol 105(3):394–398

    Article  PubMed  CAS  Google Scholar 

  • Kemal C, Louis-Flamberg P et al (1987) Reductive inactivation of soybean lipoxygenase 1 by catechols: a possible mechanism for regulation of lipoxygenase activity. Biochemistry 26(22):7064–7072

    Article  PubMed  CAS  Google Scholar 

  • Khariwala SS, Kjaergaard J et al (2006) Everolimus (RAD) inhibits in vivo growth of murine squamous cell carcinoma (SCC VII). Laryngoscope 116(5):814–820

    Article  PubMed  Google Scholar 

  • Kitano K, Nam KY et al (1997) Sealing effects of (-)-epigallocatechin gallate on protein kinase C and protein phosphatase 2A. Biophys Chem 65(2–3):157–164

    Article  PubMed  CAS  Google Scholar 

  • Kopelovich L, Fay JR et al (2007) The mammalian target of rapamycin pathway as a potential target for cancer chemoprevention. Cancer Epidemiol Biomarkers Prev 16(7):1330–1340

    Article  PubMed  CAS  Google Scholar 

  • Kress S, Sutter C et al (1992) Carcinogen-specific mutational pattern in the p53 gene in ultraviolet B radiation-induced squamous cell carcinomas of mouse skin. Cancer Res 52(22):6400–6403

    PubMed  CAS  Google Scholar 

  • Levine N, Ertl GA, Brooks C, Alberts DS (1999) Effects of a potent sythetic melanotropin, NI4 -D-Phe7-MSH (Melanotant-1) on tanning: a dose range study. J Dermatol Treat 10:127–132

    Article  CAS  Google Scholar 

  • Li JJ, Dong Z et al (1996) Inhibition of tumor promoter-induced transformation by retinoids that transrepress AP-1 without transactivating retinoic acid response element. Cancer Res 56(3):483–489

    PubMed  CAS  Google Scholar 

  • Liebenlist U, Brow K et al (1995) NF-KB: a mediator of pathogen and stress responses. In: Bseuerle PA (ed) Inducible gene expression. Birkhouser, Boston

    Google Scholar 

  • Lippman SM, Lee JS et al (1990) Biomarkers as intermediate end points in chemoprevention ­trials. J Natl Cancer Inst 82(7):555–560

    Article  PubMed  CAS  Google Scholar 

  • Lum JJ, Bauer DE et al (2005) Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120(2):237–248

    Article  PubMed  CAS  Google Scholar 

  • Marks F, Furstenberger G (2000) Cancer chemoprevention through interruption of multistage carcinogenesis. The lessons learnt by comparing mouse skin carcinogenesis and human large bowel cancer. Eur J Cancer 36(3):314–329

    Article  PubMed  CAS  Google Scholar 

  • Mathew T, Kreis H et al (2004) Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies. Clin Transplant 18(4):446–449

    Article  PubMed  Google Scholar 

  • Matsui MS, DeLeo VA (1995) Photocarcinogenesis by ultraviolet A and B. In: Mukhtar H (ed) Skin cancer: mechanisms and human relevance. CRC, Boca Raton

    Google Scholar 

  • Matsui MS, Laufer L et al (1989) Ultraviolet-B (290-320 nm)-irradiation inhibits epidermal growth-factor binding to mammalian cells. J Invest Dermatol 92(4):617–622

    Article  PubMed  CAS  Google Scholar 

  • McCormick DL, Spicer AM (1987) Nordihydroguaiaretic acid suppression of rat mammary carcinogenesis induced by N-methyl-N-nitrosourea. Cancer Lett 37(2):139–146

    Article  PubMed  CAS  Google Scholar 

  • Miller CC, Hale P et al (1994) Ultraviolet B injury increases prostaglandin synthesis through a tyrosine kinase-dependent pathway. Evidence for UVB-induced epidermal growth factor receptor activation. J Biol Chem 269(5):3529–3533

    PubMed  CAS  Google Scholar 

  • Moon TE, Levine N et al (1997) Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev 6(11):949–956

    PubMed  CAS  Google Scholar 

  • Mukhtar H, Wang ZY et al (1992) Tea components: antimutagenic and anticarcinogenic effects. Prev Med 21(3):351–360

    Article  PubMed  CAS  Google Scholar 

  • Nakadate T, Yamamoto S et al (1982) Inhibition of 12-O-tetradecanoyl-phorbol-13-acetate-induced tumor promotion by nordihydroguaiaretic acid, a lipoxygenase inhibitor, and p-bromophenacyl bromide, a phospholipase A2 inhibitor. Gann 73(6):841–843

    PubMed  CAS  Google Scholar 

  • Nakadate T, Yamamoto S et al (1985) Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced increase in vascular permeability in mouse skin by lipoxygenase inhibitors. Jpn J Pharmacol 38(2):161–168

    Article  PubMed  CAS  Google Scholar 

  • Numazawa S, Yamada H et al (1997) Cooperative induction of c-fos and heme oxygenase gene products under oxidative stress in human fibroblastic cells. Exp Cell Res 237(2):434–444

    Article  PubMed  CAS  Google Scholar 

  • O’Reilly KE, Rojo F et al (2006) mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66(3):1500–1508

    Article  PubMed  CAS  Google Scholar 

  • Odom R (1998) Managing actinic keratoses with retinoids. J Am Acad Dermatol 39(2 Pt 3): S74–S78

    Article  PubMed  CAS  Google Scholar 

  • Olsen EA, Abernethy ML et al (1991) A double-blind, vehicle-controlled study evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck. J Am Acad Dermatol 24(5 Pt 1):738–743

    Article  PubMed  CAS  Google Scholar 

  • Park S, Lee DK et al (1998) Inhibition of fos-jun-DNA complex formation by dihydroguaiaretic acid and in vitro cytotoxic effects on cancer cells. Cancer Lett 127(1–2):23–28

    Article  PubMed  CAS  Google Scholar 

  • Pentland AP, Schoggins JW et al (1999) Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis 20(10):1939–1944

    Article  PubMed  CAS  Google Scholar 

  • Pierceall WE, Goldberg LH et al (1991) Ras gene mutation and amplification in human nonmelanoma skin cancers. Mol Carcinog 4(3):196–202

    Article  PubMed  CAS  Google Scholar 

  • Pierceall WE, Kripke ML et al (1992) N-ras mutation in ultraviolet radiation-induced murine skin cancers. Cancer Res 52(14):3946–3951

    PubMed  CAS  Google Scholar 

  • Punnonen K, Yuspa SH (1992) Ultraviolet light irradiation increases cellular diacylglycerol and induces translocation of diacylglycerol kinase in murine keratinocytes. J Invest Dermatol 99(2):221–226

    Article  PubMed  CAS  Google Scholar 

  • Punnonen K, Puustinen T et al (1987) Ultraviolet B irradiation induces changes in the distribution and release of arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture. J Invest Dermatol 88(5):611–614

    Article  PubMed  CAS  Google Scholar 

  • Radler-Pohl A, Sachsenmaier C et al (1993) UV-induced activation of AP-1 involves obligatory extranuclear steps including Raf-1 kinase. EMBO J 12(3):1005–1012

    PubMed  CAS  Google Scholar 

  • Rao GN, Glasgow WC et al (1996) Role of hydroperoxyeicosatetraenoic acids in oxidative stress-induced activating protein 1 (AP-1) activity. J Biol Chem 271(44):27760–27764

    Article  PubMed  CAS  Google Scholar 

  • Rao RD, Buckner JC et al (2004) Mammalian target of rapamycin (mTOR) inhibitors as anti-cancer agents. Curr Cancer Drug Targets 4(8):621–635

    Article  PubMed  CAS  Google Scholar 

  • Rigas B, Goldman IS et al (1993) Altered eicosanoid levels in human colon cancer. J Lab Clin Med 122(5):518–523

    PubMed  CAS  Google Scholar 

  • Robertson LM, Kerppola TK et al (1995) Regulation of c-fos expression in transgenic mice requires multiple interdependent transcription control elements. Neuron 14(2):241–252

    Article  PubMed  CAS  Google Scholar 

  • Ronai ZA, Lambert ME et al (1990) Inducible cellular responses to ultraviolet light irradiation and other mediators of DNA damage in mammalian cells. Cell Biol Toxicol 6(1):105–126

    Article  PubMed  CAS  Google Scholar 

  • Rosette C, Karin M (1996) Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors. Science 274(5290):1194–1197

    Article  PubMed  CAS  Google Scholar 

  • Roymans D, Slegers H (2001) Phosphatidylinositol 3-kinases in tumor progression. Eur J Biochem 268(3):487–498

    Article  PubMed  CAS  Google Scholar 

  • Ruther U, Garber C et al (1987) Deregulated c-fos expression interferes with normal bone development in transgenic mice. Nature 325(6103):412–416

    Article  PubMed  CAS  Google Scholar 

  • Ruther U, Komitowski D et al (1989) c-fos expression induces bone tumors in transgenic mice. Oncogene 4(7):861–865

    PubMed  CAS  Google Scholar 

  • Sabatini DM (2006) mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 6(9):729–734

    Article  PubMed  CAS  Google Scholar 

  • Sachsenmaier C, Radler-Pohl A et al (1994) Involvement of growth factor receptors in the mammalian UVC response. Cell 78(6):963–972

    Article  PubMed  CAS  Google Scholar 

  • Saez E, Rutberg SE et al (1995) c-fos is required for malignant progression of skin tumors. Cell 82(5):721–732

    Article  PubMed  CAS  Google Scholar 

  • Sawyers CL (2003) Will mTOR inhibitors make it as cancer drugs? Cancer Cell 4(5):343–348

    Article  PubMed  CAS  Google Scholar 

  • Segrelles C, Ruiz S et al (2002) Functional roles of Akt signaling in mouse skin tumorigenesis. Oncogene 21(1):53–64

    Article  PubMed  CAS  Google Scholar 

  • Segrelles C, Moral M et al (2006) Molecular determinants of Akt-induced keratinocyte ­transformation. Oncogene 25(8):1174–1185

    Article  PubMed  CAS  Google Scholar 

  • Segrelles C, Lu J et al (2007) Deregulated activity of Akt in epithelial basal cells induces ­spontaneous tumors and heightened sensitivity to skin carcinogenesis. Cancer Res 67(22):10879–10888

    Article  PubMed  CAS  Google Scholar 

  • Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4(5):E131–E136

    Article  PubMed  CAS  Google Scholar 

  • Shaw RJ, Kosmatka M et al (2004) The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci USA 101(10):3329–3335

    Article  PubMed  CAS  Google Scholar 

  • Sheng H, Shao J et al (1998) Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 58(2):362–366

    PubMed  CAS  Google Scholar 

  • Skeen JE, Bhaskar PT et al (2006) Akt deficiency impairs normal cell proliferation and suppresses oncogenesis in a p53-independent and mTORC1-dependent manner. Cancer Cell 10(4):269–280

    Article  PubMed  CAS  Google Scholar 

  • Smith WL, Garavito RM et al (1996) Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 271(52):33157–33160

    Article  PubMed  CAS  Google Scholar 

  • Stratton SP, Saboda KL et al (2008) Phase 1 study of topical perillyl alcohol cream for chemoprevention of skin cancer. Nutr Cancer 60(3):325–330

    Article  PubMed  CAS  Google Scholar 

  • Strickland PT (1986) Photocarcinogenesis by near-ultraviolet (UVA) radiation in Sencar mice. J Invest Dermatol 87(2):272–275

    Article  PubMed  CAS  Google Scholar 

  • Suganuma M, Okabe S et al (1996) A new process of cancer prevention mediated through inhibition of tumor necrosis factor alpha expression. Cancer Res 56(16):3711–3715

    PubMed  CAS  Google Scholar 

  • Tang Q, Chen W et al (2001a) Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2 transcription in human keratinocytes. Oncogene 20(37):5164–5172

    Article  PubMed  CAS  Google Scholar 

  • Tang Q, Gonzales M et al (2001b) Roles of Akt and glycogen synthase kinase 3beta in the ultraviolet B induction of cyclooxygenase-2 transcription in human keratinocytes. Cancer Res 61(11):4329–4332

    PubMed  CAS  Google Scholar 

  • Tao J, Sanghera JS et al (1996) Stimulation of stress-activated protein kinase and p38 HOG1 kinase in murine keratinocytes following photodynamic therapy with benzoporphyrin derivative. J Biol Chem 271(43):27107–27115

    Article  PubMed  CAS  Google Scholar 

  • Tessman I (1976) A mechanism of UV-reactivation. In: Bukhari A, Ljungquist E (eds) Abstracts of the bacteriophage meeting. CRC, Boca Raton

    Google Scholar 

  • Thompson EJ, MacGowan J et al (2002) A dominant negative c-jun specifically blocks okadaic acid-induced skin tumor promotion. Cancer Res 62(11):3044–3047

    PubMed  CAS  Google Scholar 

  • Tornaletti S, Rozek D et al (1993) The distribution of UV photoproducts along the human p53 gene and its relation to mutations in skin cancer. Oncogene 8(8):2051–2057

    PubMed  CAS  Google Scholar 

  • Tsujii M, Kawano S et al (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93(5):705–716

    Article  PubMed  CAS  Google Scholar 

  • Vane JR, Bakhle YS et al (1998) Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 38:97–120

    Article  PubMed  CAS  Google Scholar 

  • Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2(7):489–501

    Article  PubMed  CAS  Google Scholar 

  • Wan YS, Wang ZQ et al (2001) Ultraviolet irradiation activates PI 3-kinase/AKT survival pathway via EGF receptors in human skin in vivo. Int J Oncol 18(3):461–466

    PubMed  CAS  Google Scholar 

  • Wang Y, Prywes R (2000) Activation of the c-fos enhancer by the erk MAP kinase pathway through two sequence elements: the c-fos AP-1 and p62TCF sites. Oncogene 19(11):1379–1385

    Article  PubMed  CAS  Google Scholar 

  • Wang ZY, Huang MT et al (1992) Inhibitory effect of green tea in the drinking water on tumorigenesis by ultraviolet light and 12-O-tetradecanoylphorbol-13-acetate in the skin of SKH-1 mice. Cancer Res 52(5):1162–1170

    PubMed  CAS  Google Scholar 

  • Warmuth I, Harth Y et al (1994) Ultraviolet radiation induces phosphorylation of the epidermal growth factor receptor. Cancer Res 54(2):374–36

    PubMed  CAS  Google Scholar 

  • Willis I, Menter JM et al (1981) The rapid induction of cancers in the hairless mouse utilizing the principle of photoaugmentation. J Invest Dermatol 76(5):404–408

    Article  PubMed  CAS  Google Scholar 

  • Woods A, Johnstone SR et al (2003) LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 13(22):2004–2008

    Article  PubMed  CAS  Google Scholar 

  • Wulfkuhle JD, Speer R et al (2008) Multiplexed cell signaling analysis of human breast cancer applications for personalized therapy. J Proteome Res 7(4):1508–1517

    Article  PubMed  CAS  Google Scholar 

  • Yang CS, Wang ZY (1993) Tea and cancer. J Natl Cancer Inst 85(13):1038–1049

    Article  PubMed  CAS  Google Scholar 

  • Yang CS, Lee MJ et al (1997) Polyphenols as inhibitors of carcinogenesis. Environ Health Perspect 105(Suppl 4):971–976

    Article  PubMed  CAS  Google Scholar 

  • Young MR, Li JJ et al (1999) Transgenic mice demonstrate AP-1 (activator protein-1) ­transactivation is required for tumor promotion. Proc Natl Acad Sci USA 96(17):9827–9832

    Article  PubMed  CAS  Google Scholar 

  • Yu R, Jiao JJ et al (1997) Activation of mitogen-activated protein kinases by green tea ­polyphenols: potential signaling pathways in the regulation of antioxidant-responsive element-mediated phase II enzyme gene expression. Carcinogenesis 18(2):451–456

    Article  PubMed  CAS  Google Scholar 

  • Yuspa SH (1994) The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis − thirty-third G. H. A. Clowes Memorial Award Lecture. Cancer Res 54(5):1178–1189

    PubMed  CAS  Google Scholar 

  • Zhang J, Bowden GT (2008) UVB irradiation regulates Cox-2 mRNA stability through AMPK and HuR in human keratinocytes. Mol Carcinog 47(12):974–983

    Article  PubMed  CAS  Google Scholar 

  • Zhang QS, Maddock DA et al (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. Int J Oncol 19(5):1057–1061

    PubMed  CAS  Google Scholar 

  • Ziegler A, Leffell DJ et al (1993) Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers. Proc Natl Acad Sci USA 90(9):4216–42120

    Article  PubMed  CAS  Google Scholar 

  • Ziegler A, Jonason AS et al (1994) Sunburn and p53 in the onset of skin cancer. Nature 372(6508):773–776

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell Biology and Anatomy, Arizona Cancer Centre, University of Arizona, College of Medicine, University of Arizona, Tucson, AZ, USA

    G. Tim Bowden

  2. Arizona Cancer Center, University of Arizona, Tucson, AZ, USA

    G. Tim Bowden

Authors
  1. G. Tim Bowden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David S. Alberts
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Tim Bowden .

Editor information

Editors and Affiliations

  1. Center for Molecular Toxicology &, Carcinogenesis, Pennsylvania State University, University Park, 16801, Pennsylvania, USA

    Adam B. Glick

  2. National Institute on Deafness &, Other Communication Disorders, National Institute of Health, Bethesda, 20892, Maryland, USA

    Carter Van Waes

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Bowden, G.T., Alberts, D.S. (2011). Targeting UVB Mediated Signal Transduction Pathways for the Chemoprevention of Squamous Cell Carcinoma. In: Glick, A., Waes, C. (eds) Signaling Pathways in Squamous Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7203-3_16

Download citation

Publish with us

Policies and ethics

Search

Navigation