Growth factor signaling pathways as targets for prevention of epithelial carcinogenesis

Molecular Carcinogenesis

Volumn 50, Issue 4, 2011, Pages 264-279

  Rho, Okkyung ^a   Kim, Dae Joon ^a   Kiguchi, Karou ^a   Digiovanni, John ^a  

^a UNIVERSITY OF TEXAS AT AUSTIN   (United States)

Author keywords

Akt; Epithelial carcinogenesis; Growth factor signaling; MAPK; PI3K; Src; Stat3

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR KINASE; GROWTH FACTOR RECEPTOR; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; SCATTER FACTOR RECEPTOR; SOMATOMEDIN C RECEPTOR; STAT3 PROTEIN;

ANGIOGENESIS; APOPTOSIS; ARTICLE; CANCER PREVENTION; CARCINOGENESIS; CELL ADHESION; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; EPITHELIUM CELL; HUMAN; NONHUMAN; ONCOGENE SRC; PRIORITY JOURNAL; SKIN CANCER;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; EPITHELIAL CELLS; HUMANS; MODELS, BIOLOGICAL; RECEPTOR, IGF TYPE 1; RECEPTORS, GROWTH FACTOR; SIGNAL TRANSDUCTION;

MUS MUSCULUS;

EID: 79953069592     PISSN: 08991987     EISSN: 10982744     Source Type: Journal    
DOI: 10.1002/mc.20665     Document Type: Article

References (212)

1. Abel EL, Angel JM, Kiguchi K, DiGiovanni J. Multi-stage chemical carcinogenesis in mouse skin: Fundamentals and applications. Nat Protocol 2009; 4: 1350-1362.
2. DiGiovanni J. Multistage carcinogenesis in mouse skin. Pharmacol Ther 1992; 54: 63-128.
3. Yuspa S, Dlugosz A, Cheng C, et al. Role of oncogenes and tumor suppressor genes in multistage carcinogenesis. J Invest Dermatol 1994; 103: 908-958.
4. Kemp CJ. Multistep skin cancer in mice as a model to study the evolution of cancer cells. Semin Cancer Biol 2005; 15: 460-473.
5. Fischer S, DiGiovanni J. Mechanisms of tumor promotion: Epigenetic changes in cell signaling. Cancer Bull 1995; 47: 456-463.
6. Mukhtar H. In: Mukhtar H, editor. Skin cancer: Mechanisms and human relevance. Boca Raton, FL: CRC Press; 1995.
7. DiGiovanni J. Multistage skin carcinogenesis. In: Ward J, Waalkes MP, editors. Carcinogenesis, target organ toxicology series. New York, NY: Raven Press; 1994. pp. 265-299.
8. Bowden G, Finch J, Donann F, Krieg P. Molecular mechanisms involved in skin tumor initiation, promotion, and progression. In: Mukhtar H, editor. Skin cancer: Mechanisms and human relevance. Boca Raton, FL: CRC Press; 1995. pp. 113-120.
9. Conti CJ, Aldaz CM, O'Connell J, Klein-Szanto AJ, Slaga TJ. Aneuploidy, an early event in mouse skin tumor development. Carcinogenesis 1986; 7: 1845-1848.
10. Iwatsuki M, Mimori K, Yokobori T, et al. Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci 2010; 101: 293-299.
11. Darwiche N, Ryscavage A, Perez-Lorenzo R, et al. Expression profile of skin papillomas with high cancer risk displays a unique genetic signature that clusters with squamous cell carcinomas and predicts risk for malignant conversion. Oncogene 2007; 26: 6885-6895.
12. Yates RA, Nanney LB, Gates RE, King LE, Jr. Epidermal growth factor and related growth factors. Int J Dermatol 1991; 30: 687-694.
13. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2: 127-137.
14. Nicholson RI, Hutcheson IR, Harper ME, et al. Modulation of epidermal growth factor receptor in endocrine-resistant, oestrogen receptor-positive breast cancer. Endocr Relat Cancer 2001; 8: 175-182.
15. Ullrich A, Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell 1990; 61: 203-212.
16. Aaronson SA. Growth factors and cancer. Science 1991; 254: 1146-1153.
17. Pinkas-Kramarski R, Soussan L, Waterman H, et al. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J 1996; 15: 2452-2467.
18. Ullrich A, Coussens L, Hayflick JS. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature 1984; 309: 418-424.
19. Shih C, Shilo B-Z, Godfarb M, Dannenberg A, Weinberg R. Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin. Proc Natl Acad Sci USA 1979; 76: 5714-5718.
20. Shih C, Padhy L, Murray M, Weinberg R. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature 1981; 290: 261-264.
21. Bargmann C, Hung M, Weinberg R. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature 1986; 319: 226-230.
22. Graus-Porta D, Beerli RR, Daly JM, Hynes NE. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J 1997; 16: 1647-1655.
23. Karunagaran D, Tzahar E, Beerli RR, et al. ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: Implications for breast cancer. EMBO J 1996; 15: 254-264.
24. Citri A, Skaria KB, Yarden Y. The deaf and the dumb: The biology of ErbB-2 and ErbB-3. Exp Cell Res 2003; 284: 54-65.
25. Xian W, Rosenberg MP, DiGiovanni J. Activation of erbB2 and c-src in phorbol ester-treated mouse epidermis: Possible role in mouse skin tumor promotion. Oncogene 1997; 14: 1435-1444.
26. Stoll SW, Kansra S, Peshick S, et al. Differential utilization and localization of ErbB receptor tyrosine kinases in skin compared to normal and malignant keratinocytes. Neoplasia 2001; 3: 339-350.
27. Panchal H, Wansbury O, Parry S, Ashworth A, Howard B. Neuregulin3 alters cell fate in the epidermis and mammary gland. BMC Dev Biol 2007; 7: 105.
28. Prickett TD, Agrawal NS, Wei X, et al. Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat Genet 2009; 41: 1127-1132.
29. Imamoto A, Beltran L, DiGiovanni J. Evidence of autocrine/paracrine growth stimulation by transforming growth factor α during the process of skin tumor promotion. Mol Carcinog 1991; 4: 52-60.
30. Kiguchi K, Beltran LM, You J, Rho O, DiGiovanni J. Elevation of transforming growth factor-alpha mRNA and protein expression by diverse tumor promoters in SENCAR mouse epidermis. Mol Carcinog 1995; 12: 225-235.
31. Kiguchi K, Beltran L, Rupp T, DiGiovanni J. 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. Mol Carcinog 1998; 22: 73-83.
32. Xian W, Kiguchi K, Imamoto A, Rupp T, Zilberstein A, DiGiovanni J. Activation of the epidermal growth factor receptor by skin tumor promoters and in skin tumors from SENCAR mice. Cell Growth Differ 1995; 6: 1447-1455.
33. Rho O, Beltran LM, Gimenez-Conti IB, DiGiovanni J. Altered expression of the epidermal growth factor receptor and transforming growth factor-alpha during multistage skin carcinogenesis in SENCAR mice. Mol Carcinog 1994; 11: 19-28.
34. Vassar R, Hutton M, Fuchs E. Transgenic overexpression of transforming growth factor bypasses the need for c-Ha-ras mutations in mouse skin tumorigenesis. Mol Cell Biol 1992; 12: 4643-4653.
35. Dominey AM, Wang X-J, Gagne TA. Targeted overexpression of TGFα in the epidermis of transgenic mice elicits anomalous differentiation and spontaneous, self-regressing papillomas. Cell Growth Differ 1993; 4: 1071-1082.
36. Jhappan C, Takayama H, Dickson R, Merlino G. Transgenic mice provide genetic evidence that transforming growth factor a promotes skin tumorigenesis via H-Ras-dependent and H-Ras-independent pathways. Cell Growth Differ 1994; 5: 385-394.
37. Wang XJ, Greenhalgh DA, Eckhardt JN, Rothnagel JA, Roop D. Epidermal expression of TGF-alpha in transgenic mice: Induction of spontaneous and TPA-induced papillomas via a mechanism independent of Ha-ras activation or overexpression. Mol Carcinog 1994; 10: 15-22.
38. Bol D, Kiguchi K, Beltran L, et al. Severe follicular hyperplasia and spontaneous papilloma formation in transgenic mice expressing the neu oncogene under the control of the bovine keratin 5 promoter. Mol Carcinog 1998; 21: 2-12.
39. Casanova ML, Larcher F, Casanova B, et al. A critical role for ras-mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. Cancer Res 2002; 62: 3402-3407.
40. El-Abaseri TB, Putta S, Hansen LA. Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor. Carcinogenesis 2006; 27: 225-231.
41. Madson JG, Lynch DT, Tinkum KL, Putta SK, Hansen LA. Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation. Am J Pathol 2006; 169: 1402-1414.
42. Han CY, Lim SC, Choi HS, Kang KW. Induction of ErbB2 by ultraviolet A irradiation: Potential role in malignant transformation of keratinocytes. Cancer Sci 2008; 99: 502-509.
43. Madson JG, Lynch DT, Svoboda J, et al. Erbb2 suppresses DNA damage-induced checkpoint activation and UV-induced mouse skin tumorigenesis. Am J Pathol 2009; 174: 2357-2366.
44. Song JI, Grandis JR. STAT signaling in head and neck cancer. Oncogene 2000; 19: 2489-2495.
45. Berclaz G, Altermatt HJ, Rohrbach V, Siragusa A, Dreher E, Smith PD. EGFR dependent expression of STAT3 (but not STAT1) in breast cancer. Int J Oncol 2001; 19: 1155-1160.
46. Garcia R, Bowman TL, Niu G, et al. Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 2001; 20: 2499-2513.
47. Minuto F, Del Monte P, Barreca A, et al. Evidence for an increased somatomedin-C/insulin-like growth factor 1 content in primary human lung tumors. Cancer Res 1986; 46: 985-988.
48. Yee D, Paik S, Lebovic G, et al. Analysis of insulin-like growth factor I gene expression in malignancy: Evidence for a paracrine role in human breast cancer. Mol Endocrinol 1989; 3: 509-517.
49. Kazer RR. Insulin resistance, insulin-like growth factor I and breast cancer: A hypothesis. Int J Cancer 1995; 62: 403-406.
50. Tricoli J, Rall L, Karakousis C, et al. Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas. Cancer Res 1986; 46: 6169-6173.
51. Chan JM, Stampfer MJ, Giovannucci E, et al. Plasma insulin-like growth factor-I and prostate cancer risk: A prospective study. Science 1998; 279: 563-566.
52. Peyrat JP, Bonneterre J, Hecquet B, et al. Plasma insulin-like growth factor-1 (IGF-1) concentrations in human breast cancer. Eur J Cancer 1993; 29A: 492-497.
53. Turner BC, Haffty BG, Narayanan L, et al. Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Res 1997; 57: 3079-3083.
54. Adams TE, Epa VC, Garrett TP, Ward CW. Structure and function of the type 1 insulin-like growth factor receptor. Cell Mol Life Sci 2000; 57: 1050-1093.
55. Grimberg A, Cohen P. Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol 2000; 183: 1-9.
56. Pollak M. Insulin-like growth factor physiology and cancer risk. Eur J Cancer 2000; 36: 1224-1228.
57. Ullrich A, Gray A, Tam AW, et al. Insulin-like growth factor I receptor primary structure: Comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J 1986; 5: 2503-2512.
58. Lowe WL. Biological actions of the insulin-like growth factors. In: LeRoith D, editor. Insulin-like growth factors: Molecular and cellular aspects. Boca Raton, FL: CRC Press; 1991. pp. 49-85.
59. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: Biological actions. Endocrine Rev 1995; 16: 3-34.
60. Werner H, Le Roith D. New concepts in regulation and function of the insulin-like growth factors: Implications for understanding normal growth and neoplasia. Cell Mol Life Sci 2000; 57: 932-942.
61. Parrizas M, LeRoith D. Insulin-like growth factor-1 inhibition of apoptosis is associated with increased expression of the bcl-xL gene product. Endocrinology 1997; 138: 1355-1358.
62. Liscovitch M, Cantley LC. Lipid second messengers. Cell 1994; 77: 329-334.
63. Kulik G, Klippel A, Weber M. Anti-apoptotic signaling by the insulin-like growth factor-1 receptor, phosphatidylinositol 3-kinase and AKT. Mol Cell Biol 1997; 17: 1595-1606.
64. Ahmed NN, Grimes HL, Bellacosa A, Chan TO, Tsichlis PN. Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. Proc Natl Acad Sci USA 1997; 94: 3627-3632.
65. Kennedy SG, Wagner AJ, Conzen SD, et al. The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev 1997; 11: 701-713.
66. Marte BM, Downward J. PKB/Akt: Connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem Sci 1997; 22: 355-358.
67. DiGiovanni J, Bol DK, Wilker E, et al. Constitutive expression of insulin-like growth factor-1 in epidermal basal cells of transgenic mice leads to spontaneous tumor promotion. Cancer Res 2000; 60: 1561-1570.
68. Wilker E, Lu J, Rho O, Carbajal S, Beltran L, DiGiovanni J. Role of PI3K/Akt signaling in insulin-like growth factor-1 (IGF-1) skin tumor promotion. Mol Carcinog 2005; 44: 137-145.
69. Bol D, Kiguchi K, Gimenez-Conti I, Rupp T, DiGiovanni J. Overexpression of insulin-like growth factor-1 induces hyperplasia, dermal abnormalities, and spontaneous tumor formation in transgenic mice. Oncogene 1997; 14: 1725-1734.
70. Moore T, Carbajal S, Beltran L, et al. Reduced susceptibility to two-stage skin carcinogenesis in mice with low circulating IGF-1 levels. Cancer Res 2008; 68: 3680-3688.
71. Dean M, Park M, Le Beau MM, et al. The human met oncogene is related to the tyrosine kinase oncogenes. Nature 1985; 318: 385-388.
72. Nakamura T, Nawa K, Ichihara A. Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem Biophys Res Commun 1984; 122: 1450-1459.
73. Bottaro DP, Rubin JS, Faletto DL, et al. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 1991; 251: 802-804.
74. Stoker M, Gherardi E, Perryman M, Gray J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature 1987; 327: 239-242.
75. Weidner KM, Behrens J, Vandekerckhove J, Birchmeier W. Scatter factor: Molecular characteristics and effect on the invasiveness of epithelial cells. J Cell Biol 1990; 111: 2097-2108.
76. Gherardi E, Sandin S, Petoukhov MV, et al. Structural basis of hepatocyte growth factor/scatter factor and MET signalling. Proc Natl Acad Sci USA 2006; 103: 4046-4051.
77. Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. Met, metastasis, motility and more. Nat Rev Mol Cell Biol 2003; 4: 915-925.
78. Bertotti A, Burbridge MF, Gastaldi S, et al. Only a subset of met-activated pathways are required to sustain oncogene addiction. Sci Signal 2009; 2: er11.
79. Igawa T, Kanda S, Kanetake H, et al. Hepatocyte growth factor is a potent mitogen for cultured rabbit renal tubular epithelial cells. Biochem Biophys Res Commun 1991; 174: 831-838.
80. Kan M, Zhang GH, Zarnegar R, et al. Hepatocyte growth factor/hepatopoietin A stimulates the growth of rat kidney proximal tubule epithelial cells (RPTE), rat nonparenchymal liver cells, human melanoma cells, mouse keratinocytes and stimulates anchorage-independent growth of SV-40 transformed RPTE. Biochem Biophys Res Commun 1991; 174: 331-337.
81. Matsumoto K, Tajima H, Nakamura T. Hepatocyte growth factor is a potent stimulator of human melanocyte DNA synthesis and growth. Biochem Biophys Res Commun 1991; 176: 45-51.
82. Olivero M, Rizzo M, Madeddu R, et al. Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas. Br J Cancer 1996; 74: 1862-1868.
83. Tuck AB, Park M, Sterns EE, Boag A, Elliott BE. Coexpression of hepatocyte growth factor and receptor (Met) in human breast carcinoma. Am J Pathol 1996; 148: 225-232.
84. Nayeri F, Xu J, Abdiu A, et al. Autocrine production of biologically active hepatocyte growth factor (HGF) by injured human skin. J Dermatol Sci 2006; 43: 49-56.
85. Chmielowiec J, Borowiak M, Morkel M, et al. c-Met is essential for wound healing in the skin. J Cell Biol 2007; 177: 151-162.
86. Nakamura Y, Matsubara D, Goto A, et al. Constitutive activation of c-Met is correlated with c-Met overexpression and dependent on cell-matrix adhesion in lung adenocarcinoma cell lines. Cancer Sci 2008; 99: 14-22.
87. Otsuka T, Takayama H, Sharp R, et al. c-Met autocrine activation induces development of malignant melanoma and acquisition of the metastatic phenotype. Cancer Res 1998; 58: 5157-5167.
88. Noonan FP, Otsuka T, Bang S, Anver MR, Merlino G. Accelerated ultraviolet radiation-induced carcinogenesis in hepatocyte growth factor/scatter factor transgenic mice. Cancer Res 2000; 60: 3738-3743.
89. Mildner M, Eckhart L, Lengauer B, Tschachler E. Hepatocyte growth factor/scatter factor inhibits UVB-induced apoptosis of human keratinocytes but not of keratinocyte-derived cell lines via the phosphatidylinositol 3-kinase/AKT pathway. J Biol Chem 2002; 277: 14146-14152.
90. Mazzone M, Basilico C, Cavassa S, et al. An uncleavable form of pro-scatter factor suppresses tumor growth and dissemination in mice. J Clin Invest 2004; 114: 1418-1432.
91. Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007; 316: 1039-1043.
92. Lai AZ, Abella JV, Park M. Crosstalk in Met receptor oncogenesis. Trends Cell Biol 2009; 19: 542-551.
93. Ronsin C, Muscatelli F, Mattei MG, Breathnach R. A novel putative receptor protein tyrosine kinase of the met family. Oncogene 1993; 8: 1195-1202.
94. Gaudino G, Follenzi A, Naldini L, et al. RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. EMBO J 1994; 13: 3524-3532.
95. Follenzi A, Bakovic S, Gual P, Stella MC, Longati P, Comoglio PM. Cross-talk between the proto-oncogenes Met and Ron. Oncogene 2000; 19: 3041-3049.
96. Chan EL, Peace BE, Collins MH, Toney-Earley K, Waltz SE. Ron tyrosine kinase receptor regulates papilloma growth and malignant conversion in a murine model of skin carcinogenesis. Oncogene 2005; 24: 479-488.
97. Brugge JS, Erikson RL. Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature 1977; 269: 346-348.
98. Collett M, Erikson E, Purchio AF, Brugge JS, Erikson RL. A normal cell protein similar in structure and function to the avian sarcoma virus transforming gene product. Proc Natl Acad Sci USA 1979; 76: 3159-3163.
99. Okada M, Nakagawa H. Identification of a novel protein tyrosine kinase that phosphorylates pp60c-src and regulates its activity in neonatal rat brain. Biochem Biophys Res Commun 1988; 154: 796-802.
100. rc family of protein-tyrosine kinases: Structure, regulation, and function. Crit Rev Oncog 1992; 3: 401-446.
101. Brown MT, Cooper JA. Regulation, substrates and functions of src. Biochem Biophys Acta 1996; 1287: 121-149.
102. Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: A model for targeted therapy. Clin Cancer Res 2006; 12: 5268-5272.
103. Yeatman TJ. A renaissance for SRC. Nat Rev Cancer 2004; 4: 470-480.
104. Summy JM, Gallick GE. Treatment for advanced tumors: SRC reclaims center stage. Clin Cancer Res 2006; 12: 1398-1401.
105. Courtneidge SA. Role of Src in signal transduction pathways. The Jubilee Lecture. Biochem Soc Trans 2002; 30: 11-17.
106. Irby RB, Yeatman TJ. Role of Src expression and activation in human cancer. Oncogene 2000; 19: 5636-5642.
107. Wheeler DL, Iida M, Dunn EF. The role of Src in solid tumors. Oncologist 2009; 14: 667-678.
108. Summy JM, Gallick GE. Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev 2003; 22: 337-358.
109. Barnekow A, Paul E, Schartl M. Expression of the c-src protooncogene in human skin tumors. Cancer Res 1987; 47: 235-240.
110. O'Connor TJ, Bjorge JD, Cheng HC, Wang JH, Fujita DJ. Mechanism of c-SRC activation in human melanocytes: Elevated level of protein tyrosine phosphatase activity directed against the carboxy-terminal regulatory tyrosine. Cell Growth Differ 1995; 6: 123-130.
111. Matsumoto T, Jiang J, Kiguchi K, et al. Targeted expression of c-Src in epidermal basal cells leads to enhanced skin tumor promotion, malignant progression, and metastasis. Cancer Res 2003; 63: 4819-4828.
112. Matsumoto T, Kiguchi K, Jiang J, et al. Development of transgenic mice that inducibly express an active form of c-Src in the epidermis. Mol Carcinog 2004; 40: 189-200.
113. Matsumoto T, Jiang J, Kiguchi K, et al. Overexpression of a constitutively active form of c-src in skin epidermis increases sensitivity to tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Mol Carcinog 2002; 33: 146-155.
114. Darnell JE, Jr. STATs and gene regulation. Science 1997; 277: 1630-1635.
115. Levy DE, Lee CK. What does Stat3 do? J Clin Invest 2002; 109: 1143-1148.
116. Akira S. Functional roles of STAT family proteins: Lessons from knockout mice. Stem Cells 1999; 17: 138-146.
117. Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 2002; 285: 1-24.
118. Haura EB, Turkson J, Jove R. Mechanisms of disease: Insights into the emerging role of signal transducers and activators of transcription in cancer. Nat Clin Pract Oncol 2005; 2: 315-324.
119. Kiuchi N, Nakajima K, Ichiba M, et al. STAT3 is required for the gp130-mediated full activation of the c-myc gene. J Exp Med 1999; 189: 63-73.
120. Sinibaldi D, Wharton W, Turkson J, Bowman T, Pledger WJ, Jove R. Induction of p21WAF1/CIP1 and cyclin D1 expression by the Src oncoprotein in mouse fibroblasts: Role of activated STAT3 signaling. Oncogene 2000; 19: 5419-5427.
121. Leslie K, Lang C, Devgan G, et al. Cyclin D1 is transcriptionally regulated by and required for transformation by activated signal transducer and activator of transcription 3. Cancer Res 2006; 66: 2544-2552.
122. Epling-Burnette PK, Liu JH, Catlett-Falcone R, et al. Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J Clin Invest 2001; 107: 351-362.
123. Gritsko T, Williams A, Turkson J, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res 2006; 12: 11-19.
124. Catlett-Falcone R, Landowski TH, Oshiro MM, et al. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 1999; 10: 105-115.
125. Real PJ, Sierra A, De Juan A, Segovia JC, Lopez-Vega JM, Fernandez-Luna JL. Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells. Oncogene 2002; 21: 7611-7618.
126. Alvarez JV, Febbo PG, Ramaswamy S, Loda M, Richardson A, Frank DA. Identification of a genetic signature of activated signal transducer and activator of transcription 3 in human tumors. Cancer Res 2005; 65: 5054-5062.
127. Xie TX, Wei D, Liu M, et al. Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene 2004; 23: 3550-3560.
128. Itoh M, Murata T, Suzuki T, et al. Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells. Oncogene 2006; 25: 1195-1204.
129. Bromberg JF. Activation of STAT proteins and growth control. Bioessays 2001; 23: 161-169.
130. Buettner R, Mora LB, Jove R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 2002; 8: 945-954.
131. Jing N, Tweardy DJ. Targeting Stat3 in cancer therapy. Anticancer Drugs 2005; 16: 601-607.
132. Sano S, Chan KS, Kira M, et al. Signal transducer and activator of transcription 3 is a key regulator of keratinocyte survival and proliferation following UV irradiation. Cancer Res 2005; 65: 5720-5729.
133. Grandis JR, Drenning SD, Chakraborty A, et al. Requirement of Stat3 but not Stat1 activation for epidermal growth factor receptor-mediated cell growth in vitro. J Clin Invest 1998; 102: 1385-1392.
134. Takeda K, Noguchi K, Shi W, et al. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci USA 1997; 94: 3801-3804.
135. Sano S, Itami S, Takeda K, et al. Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis. EMBO J 1999; 18: 4657-4668.
136. Sano S, Chan KS, Digiovanni J. Impact of Stat3 activation upon skin biology: A dichotomy of its role between homeostasis and diseases. J Dermatol Sci 2008; 50: 1-14.
137. Kim DJ, Chan KS, Sano S, Digiovanni J. Signal transducer and activator of transcription 3 (Stat3) in epithelial carcinogenesis. Mol Carcinog 2007; 46: 725-731.
138. Chan KS, Sano S, Kiguchi K, et al. Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis. J Clin Invest 2004; 114: 720-728.
139. Kim DJ, Kataoka K, Rao D, Kiguchi K, Cotsarelis G, Digiovanni J. Targeted disruption of stat3 reveals a major role for follicular stem cells in skin tumor initiation. Cancer Res 2009; 69: 7587-7594.
140. Kataoka K, Kim DJ, Carbajal S, Clifford JL, DiGiovanni J. Stage-specific disruption of Stat3 demonstrates a direct requirement during both the initiation and promotion stages of mouse skin tumorigenesis. Carcinogenesis 2008; 29: 1108-1114.
141. Chan KS, Sano S, Kataoka K, et al. Forced expression of a constitutively active form of Stat3 in mouse epidermis enhances malignant progression of skin tumors induced by two-stage carcinogenesis. Oncogene 2008; 27: 1087-1094.
142. Ahsan H, Aziz MH, Ahmad N. Ultraviolet B exposure activates Stat3 signaling via phosphorylation at tyrosine705 in skin of SKH1 hairless mouse: A target for the management of skin cancer? Biochem Biophys Res Commun 2005; 333: 241-246.
143. Aziz MH, Manoharan HT, Verma AK. Protein kinase C epsilon, which sensitizes skin to sun's UV radiation-induced cutaneous damage and development of squamous cell carcinomas, associates with Stat3. Cancer Res 2007; 67: 1385-1394.
144. Barton BE, Karras JG, Murphy TF, Barton A, Huang HF. Signal transducer and activator of transcription 3 (STAT3) activation in prostate cancer: Direct STAT3 inhibition induces apoptosis in prostate cancer lines. Mol Cancer Ther 2004; 3: 11-20.
145. Nam S, Buettner R, Turkson J, et al. Indirubin derivatives inhibit Stat3 signaling and induce apoptosis in human cancer cells. Proc Natl Acad Sci USA 2005; 102: 5998-6003.
146. Turkson J, Zhang S, Mora LB, Burns A, Sebti S, Jove R. A novel platinum compound inhibits constitutive Stat3 signaling and induces cell cycle arrest and apoptosis of malignant cells. J Biol Chem 2005; 280: 32979-32988.
147. Turkson J. STAT proteins as novel targets for cancer drug discovery. Expert Opin Ther Targets 2004; 8: 409-422.
148. Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol 2006; 71: 1397-1421.
149. Bharti AC, Donato N, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol 2003; 171: 3863-3871.
150. Masuda M, Suzui M, Weinstein IB. Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clin Cancer Res 2001; 7: 4220-4229.
151. Wung BS, Hsu MC, Wu CC, Hsieh CW. Resveratrol suppresses IL-6-induced ICAM-1 gene expression in endothelial cells: Effects on the inhibition of STAT3 phosphorylation. Life Sci 2005; 78: 389-397.
152. Ghosh AK, Kay NE, Secreto CR, Shanafelt TD. Curcumin inhibits prosurvival pathways in chronic lymphocytic leukemia B cells and may overcome their stromal protection in combination with EGCG. Clin Cancer Res 2009; 15: 1250-1258.
153. Huang MT, Ma W, Lu YP, et al. Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion. Carcinogenesis 1995; 16: 2493-2497.
154. Kapadia GJ, Azuine MA, Tokuda H, et al. Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis. Pharmacol Res 2002; 45: 499-505.
155. Manning BD, Cantley LC. AKT/PKB signaling: Navigating downstream. Cell 2007; 129: 1261-1274.
156. Crowell JA, Steele VE, Fay JR. Targeting the AKT protein kinase for cancer chemoprevention. Mol Cancer Ther 2007; 6: 2139-2148.
157. Chan TO, Rittenhouse SE, Tsichlis PN. AKT/PKB and other D3 phosphoinositide-regulated kinases: Kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem 1999; 68: 965-1014.
158. Stephens L, Anderson K, Stokoe D, et al. Protein kinase B kinases that mediate phosphatidylinositol 3, 4, 5-trisphosphate-dependent activation of protein kinase B. Science 1998; 279: 710-714.
159. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006; 7: 606-619.
160. Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: Rationale and promise. Cancer Cell 2003; 4: 257-262.
161. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 2006; 441: 424-430.
162. Jacinto E, Facchinetti V, Liu D, et al. SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 2006; 127: 125-137.
163. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002; 2: 489-501.
164. Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: The PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 2006; 6: 184-192.
165. Segrelles C, Ruiz S, Perez P, et al. Functional roles of Akt signaling in mouse skin tumorigenesis. Oncogene 2002; 21: 53-64.
166. Segrelles C, Moral M, Lara MF, et al. Molecular determinants of Akt-induced keratinocyte transformation. Oncogene 2006; 25: 1174-1185.
167. Affara NI, Schanbacher BL, Mihm MJ, et al. Activated Akt-1 in specific cell populations during multi-stage skin carcinogenesis. Anticancer Res 2004; 24: 2773-2781.
168. Affara NI, Trempus CS, Schanbacher BL, et al. Activation of Akt and mTOR in CD34+/K15+ keratinocyte stem cells and skin tumors during multi-stage mouse skin carcinogenesis. Anticancer Res 2006; 26: 2805-2820.
169. Lu J, Rho O, Wilker E, Beltran L, DiGiovanni J. Activation of epidermal Akt by diverse mouse skin tumor promotion. Molecular Cancer Res 2007; 1342-1352.
170. Segrelles C, Lu J, Hammann B, et al. Deregulated activity of Akt in basal cells of stratified epithelia induces spotaneous tumors and heightened sensitivity to skin carcinogenesis. Cancer Res 2007; 67: 10879-10888.
171. Andjelkovic M, Jakubowicz T, Cron P, Ming XF, Han JW, Hemmings BA. Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors. Proc Natl Acad Sci USA 1996; 93: 5699-5704.
172. Corradetti MN, Guan KL. Upstream of the mammalian target of rapamycin: Do all roads pass through mTOR? Oncogene 2006; 25: 6347-6360.
173. Amornphimoltham P, Patel V, Sodhi A, et al. Mammalian target of rapamycin, a molecular target in squamous cell carcinomas of the head and neck. Cancer Res 2005; 65: 9953-9961.
174. Kopelovich L, Fay JR, Sigman CC, Crowell JA. The mammalian target of rapamycin pathway as a potential target for cancer chemoprevention. Cancer Epidemiol Biomarkers Prev 2007; 16: 1330-1340.
175. Yoon S, Seger R. The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions. Growth Factors 2006; 24: 21-44.
176. Murphy LO, Blenis J. MAPK signal specificity: The right place at the right time. Trends Biochem Sci 2006; 31: 268-275.
177. Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene 2007; 26: 3279-3290.
178. Khokhlatchev AV, Canagarajah B, Wilsbacher J, et al. Phosphorylation of the MAP kinase ERK2 promotes its homodimerization and nuclear translocation. Cell 1998; 93: 605-615.
179. Esteban LM, Vicario-Abejon C, Fernandez-Salguero P, et al. Targeted genomic disruption of H-ras and N-ras, individually or in combination, reveals the dispensability of both loci for mouse growth and development. Mol Cell Biol 2001; 21: 1444-1452.
180. Ise K, Nakamura K, Nakao K, et al. Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis. Oncogene 2000; 19: 2951-2956.
181. Umanoff H, Edelmann W, Pellicer A, Kucherlapati R. The murine N-ras gene is not essential for growth and development. Proc Natl Acad Sci USA 1995; 92: 1709-1713.
182. Johnson L, Greenbaum D, Cichowski K, et al. K-ras is an essential gene in the mouse with partial functional overlap with N-ras. Genes Dev 1997; 11: 2468-2481.
183. Pritchard CA, Bolin L, Slattery R, Murray R, McMahon M. Post-natal lethality and neurological and gastrointestinal defects in mice with targeted disruption of the A-Raf protein kinase gene. Curr Biol 1996; 6: 614-617.
184. Wojnowski L, Zimmer AM, Beck TW, et al. Endothelial apoptosis in Braf-deficient mice. Nat Genet 1997; 16: 293-297.
185. Wojnowski L, Stancato LF, Zimmer AM, et al. Craf-1 protein kinase is essential for mouse development. Mech Dev 1998; 76: 141-149.
186. Belanger LF, Roy S, Tremblay M, et al. Mek2 is dispensable for mouse growth and development. Mol Cell Biol 2003; 23: 4778-4787.
187. Giroux S, Tremblay M, Bernard D, et al. Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta. Curr Biol 1999; 9: 369-372.
188. Hatano N, Mori Y, Oh-hora M, et al. Essential role for ERK2 mitogen-activated protein kinase in placental development. Genes Cells 2003; 8: 847-856.
189. Saba-El-Leil MK, Vella FD, Vernay B, et al. An essential function of the mitogen-activated protein kinase Erk2 in mouse trophoblast development. EMBO Rep 2003; 4: 964-968.
190. Pages G, Guerin S, Grall D, et al. Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice. Science 1999; 286: 1374-1377.
191. Scholl FA, Dumesic PA, Barragan DI, et al. Mek1/2 MAPK kinases are essential for mammalian development, homeostasis, and Raf-induced hyperplasia. Dev Cell 2007; 12: 615-629.
192. Scholl FA, Dumesic PA, Barragan DI, Harada K, Charron J, Khavari PA. Selective role for Mek1 but not Mek2 in the induction of epidermal neoplasia. Cancer Res 2009; 69: 3772-3778.
193. Bourcier C, Jacquel A, Hess J, et al. p44 mitogen-activated protein kinase (extracellular signal-regulated kinase 1)-dependent signaling contributes to epithelial skin carcinogenesis. Cancer Res 2006; 66: 2700-2707.
194. Tarutani M, Cai T, Dajee M, Khavari PA. Inducible activation of Ras and Raf in adult epidermis. Cancer Res 2003; 63: 319-323.
195. Scholl FA, Dumesic PA, Khavari PA. Mek1 alters epidermal growth and differentiation. Cancer Res 2004; 64: 6035-6040.
196. Feith DJ, Bol DK, Carboni JM, et al. Induction of ornithine decarboxylase activity is a necessary step for mitogen-activated protein kinase kinase-induced skin tumorigenesis. Cancer Res 2005; 65: 572-578.
197. Gill RD, Beltran L, Nettikumara AN, Kootstra A, DiGiovanni J. Analysis of point mutations in murine Ha-ras from tumors initiated with dibenz[a, j]anthracene and its derivatives. Mol Carcinog 1992; 6: 53-59.
198. Angel P, Karin M. The role of Jun, Fos, and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1991; 1072: 129-157.
199. Bernstein LR, Colburn NH. AP1/jun function is differentially induced in promotion-sensitive and resistant JB6 cells. Science 1989; 244: 566-569.
200. Papavassiliou AG, Treier M, Bohmann D. Intramolecular signal transduction in c-Jun. EMBO J 1995; 14: 2014-2019.
201. Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol 2002; 4: E131-136.
202. Domann FE, Levy JP, Birrer MJ, Bowden GT. Stable expression of a c-JUN deletion mutant in two malignant mouse epidermal cell lines blocks tumor formation in nude mice. Cell Growth Differ 1994; 5: 9-16.
203. Dong Z, Crawford HC, Lavrovsky V, et al. A dominant negative mutant of jun blocking 12-O-tetradecanoylphorbol-13-acetate-induced invasion in mouse keratinocytes. Mol Carcinog 1997; 19: 204-212.
204. Li JJ, Rhim JS, Schlegel R, Vousden KH, Colburn NH. Expression of dominant negative Jun inhibits elevated AP-1 and NF-kappaB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes. Oncogene 1998; 16: 2711-2721.
205. Young MR, Li JJ, Rincon M, et al. Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion. Proc Natl Acad Sci USA 1999; 96: 9827-9832.
206. Thompson EJ, MacGowan J, Young MR, Colburn N, Bowden GT. A dominant negative c-jun specifically blocks okadaic acid-induced skin tumor promotion. Cancer Res 2002; 62: 3044-3047.
207. Cooper SJ, MacGowan J, Ranger-Moore J, Young MR, Colburn NH, Bowden GT. 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 2003; 1: 848-854.
208. Wei Q, Jiang H, Matthews CP, Colburn NH. Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin malignancies. Proc Natl Acad Sci USA 2008; 105: 19738-19743.
209. Matthews CP, Birkholz AM, Baker AR, et al. Dominant-negative activator protein 1 (TAM67) targets cyclooxygenase-2 and osteopontin under conditions in which it specifically inhibits tumorigenesis. Cancer Res 2007; 67: 2430-2438.
210. Dhar A, Hu J, Reeves R, Resar LM, Colburn NH. Dominant-negative c-Jun (TAM67) target genes: HMGA1 is required for tumor promoter-induced transformation. Oncogene 2004; 23: 4466-4476.
211. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003; 3: 11-22.
212. Hoshino R, Chatani Y, Yamori T, et al. Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors. Oncogene 1999; 18: 813-822.