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Melanoma Development and Pigment Cell Transformation

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Book cover From Melanocytes to Melanoma

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Abstract

The unique nature of a melanocyte is based on its capacity to respond to ultraviolet (UV) radiation with the production of melanin-containing melanosomes, which subsequently are transferred to adjacent keratinocytes to deliver a protective shield. Besides the specific expression of some melanogenesis-related genes, a melanocyte is equipped with an elevated level of antiapoptotic activities, which seems to enhance the threshold for UV-induced apoptosis in this cell type. A further response to UV exposure of the skin is the induction of mitogenic activities and a subsequent increase in the number of melanocytes, which is reflected in the existence of acquired nevi. Melanocytes originate from cells with a high migratory activity and they can react to UV radiation by migration into deeper dermal layers of the skin. Thus, because antiapoptotic, mitogenic, and migratory activities can easily be induced in a melanocyte, it is a sensitive target for factors disturbing its physiological homeostasis and it might also explain why the transformation of melanocytes leads to such highly aggressive tumor cells.

The coordinated balance of differentiation, proliferation, and apoptosis is a prerequisite for the maintenance of cellular homeostasis. Understanding the signaling pathways and molecules involved in the regulation of melanocyte biology and finding the factors that lead to deregulation and ultimately to the transformation of a pigment cell will help in understanding melanoma development. Today, more and more pigment cell-specific-signaling pathways, whose relevance is also reflected in the genetics of melanoma, have been discovered. In the following chapter, some of the signaling pathways that are important for physiological processes in melanocytes, a nd which have been shown to be deregulated in melanoma cells, are discussed.

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References

  1. Lazar-Molnar E, Hegyesi H, Toth S, Falus A. Autocrine and paracrine regulation by cytokines and growth factors in melanoma. Cytokine 2000;12:547–554.

    Article  PubMed  CAS  Google Scholar 

  2. Luger TA, Scholzen T, Grabbe S. The role of alpha-melanocyte-stimulating hormone in cutaneous biology. J Investig Dermatol Symp Proc 1997;2:87–93.

    PubMed  CAS  Google Scholar 

  3. Busca R, Ballotti R. Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res 2000;13:60–69.

    Article  PubMed  CAS  Google Scholar 

  4. Bentley NJ, Eisen T, Goding CR. Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiator. Mol Cell Biol 1994;14:7996–8006.

    PubMed  CAS  Google Scholar 

  5. Bertolotto C, Bille K, Ortonne JP, Ballotti R. Regulation of tyrosinase gene expression by cAMP in B16 melanoma cells involves two CATGTG motifs surrounding the TATA box: implication of the microphthalmia gene product. J Cell Biol 1996;134:747–755.

    Article  PubMed  CAS  Google Scholar 

  6. Yavuzer U, Keenan E, Lowings P, Vachtenheim J, Currie G, Goding CR. The Microphthalmia gene product interacts with the retinoblastoma protein in vitro and is a target for deregulation of melanocyte-specific transcription. Oncogene 1995;10:123–134.

    PubMed  CAS  Google Scholar 

  7. Bertolotto C, Abbe P, Hemesath TJ, et al. Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes. J Cell Biol 1998;142:827–835.

    Article  PubMed  CAS  Google Scholar 

  8. Price ER, Horstmann MA, Wells AG, et al. alpha-Melanocyte-stimulating hormone signaling regulates expression of microphthalmia, a gene deficient in Waardenburg syndrome. J Biol Chem 1998;273:33,042–33,047.

    Article  PubMed  CAS  Google Scholar 

  9. Imokawa G, Miyagishi M, Yada Y. Endothelin-1 as a new melanogen: coordinated expression of its gene and the tyrosinase gene in UVB-exposed human epidermis. J Invest Dermatol 1995;105:32–37.

    Article  PubMed  CAS  Google Scholar 

  10. Tada A, Suzuki I, Im S, et al. Endothelin-1 is a paracrine growth factor that modulates melanogenesis of human melanocytes and participates in their responses to ultraviolet radiation. Cell Growth Differ 1998;9:575–584.

    PubMed  CAS  Google Scholar 

  11. Grichnik JM, Burch JA, Burchette J, Shea CR. The SCF/KIT pathway plays a critical role in the control of normal human melanocyte homeostasis. J Invest Dermatol 1998;111:233–238.

    Article  PubMed  CAS  Google Scholar 

  12. Galibert MD, Carreira S, Goding CR. The Usf-1 transcription factor is a novel target for the stressresponsive p38 kinase and mediates UV-induced Tyrosinase expression. Embo J 2001;20:5022–5031.

    Article  PubMed  CAS  Google Scholar 

  13. Smalley K, Eisen T. The involvement of p38 mitogen-activated protein kinase in the alpha-melanocyte stimulating hormone (alpha-MSH)-induced melanogenic and anti-proliferative effects in B16 murine melanoma cells. FEBS Lett 2000;476:198–202.

    Article  PubMed  CAS  Google Scholar 

  14. Grichnik JM, Ali WN, Burch JA, et al. KIT expression reveals a population of precursor melanocytes in human skin. J Invest Dermatol 1996;106:967–971.

    Article  PubMed  CAS  Google Scholar 

  15. Kawaguchi Y, Mori N, Nakayama A. Kit(+) melanocytes seem to contribute to melanocyte proliferation after UV exposure as precursor cells. J Invest Dermatol 2001;116:920–925.

    Article  PubMed  CAS  Google Scholar 

  16. Imokawa G, Yada Y, Kimura M. Signalling mechanisms of endothelin-induced mitogenesis and melanogenesis in human melanocytes. Biochem J 1996;314:305–312.

    PubMed  CAS  Google Scholar 

  17. Hachiya A, Kobayashi A, Ohuchi A, Takema Y, Imokawa G. The paracrine role of stem cell factor/ c-kit signaling in the activation of human melanocytes in ultraviolet-B-induced pigmentation. J Invest Dermatol 2001;116:578–586.

    Article  PubMed  CAS  Google Scholar 

  18. De Luca M, Siegrist W, Bondanza S, Mathor M, Cancedda R, Eberle AN. Alpha melanocyte stimulating hormone (alpha MSH) stimulates normal human melanocyte growth by binding to highaffinity receptors. J Cell Sci 1993;105(Pt 4):1079–1084.

    PubMed  Google Scholar 

  19. Bohm M, Moellmann G, Cheng E, et al. Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes. Cell Growth Differ 1995;6:291–302.

    PubMed  CAS  Google Scholar 

  20. Imokawa G, Kobayasi T, Miyagishi M. Intracellular signaling mechanisms leading to synergistic effects of endothelin-1 and stem cell factor on proliferation of cultured human melanocytes. Crosstalk via trans-activation of the tyrosine kinase c-kit receptor. J Biol Chem 2000;275:33,321–33,328.

    Article  PubMed  CAS  Google Scholar 

  21. Swope VB, Medrano EE, Smalara D, Abdel-Malek ZA. Long-term proliferation of human melanocytes is supported by the physiologic mitogens alpha-melanotropin, endothelin-1, and basic fibroblast growth factor. Exp Cell Res 1995;217:453–459.

    Article  PubMed  CAS  Google Scholar 

  22. Bastian BC. Understanding the progression of melanocytic neoplasia using genomic analysis: from fields to cancer. Oncogene 2003;22:3081–3086.

    Article  PubMed  CAS  Google Scholar 

  23. Bennett DC. Human melanocyte senescence and melanoma susceptibility genes. Oncogene 2003;22:3063–3069.

    Article  PubMed  CAS  Google Scholar 

  24. Meier F, Satyamoorthy K, Nesbit M, et al. Molecular events in melanoma development and progression. Front Biosci 1998;3:D1005–D1010.

    PubMed  CAS  Google Scholar 

  25. Hayward N. New developments in melanoma genetics. Curr Oncol Rep 2000;2:300–306.

    Article  PubMed  CAS  Google Scholar 

  26. Witte ON. Steel locus defines new multipotent growth factor. Cell 1990;63:5,6.

    Article  PubMed  CAS  Google Scholar 

  27. Manova K, Bachvarova RF. Expression of c-kit encoded at the W locus of mice in developing embryonic germ cells and presumptive melanoblasts. Dev Biol 1991;146:312–324.

    Article  PubMed  CAS  Google Scholar 

  28. Fleischman RA. From white spots to stem cells: the role of the Kit receptor in mammalian development. Trends Genet 1993;9:285–290.

    Article  PubMed  CAS  Google Scholar 

  29. Zhai S, Yaar M, Doyle SM, Gilchrest BA. Nerve growth factor rescues pigment cells from ultravioletinduced apoptosis by upregulating BCL-2 levels. Exp Cell Res 1996;224:335–343.

    Article  PubMed  CAS  Google Scholar 

  30. Kadekaro AL, Kanto H, Kavanagh R, Abdel-Malek ZA. Significance of the melanocortin 1 receptor in regulating human melanocyte pigmentation, proliferation, and survival. Ann N Y Acad Sci 2003;994:359–365.

    Article  PubMed  CAS  Google Scholar 

  31. Alanko T, Rosenberg M, Saksela O. FGF expression allows nevus cells to survive in three-dimensional collagen gel under conditions that induce apoptosis in normal human melanocytes. J Invest Dermatol 1999;113:111–116.

    Article  PubMed  CAS  Google Scholar 

  32. Ahmed NU, Ueda M, Ito A, Ohashi A, Funasaka Y, Ichihashi M. Expression of fibroblast growth factor receptors in naevus-cell naevus and malignant melanoma. Melanoma Res 1997;7:299–305.

    Article  PubMed  CAS  Google Scholar 

  33. Ueda M, Funasaka Y, Ichihashi M, Mishima Y. Stable and strong expression of basic fibroblast growth factor in naevus cell naevus contrasts with aberrant expression in melanoma. Br J Dermatol 1994;130:320–324.

    Article  PubMed  CAS  Google Scholar 

  34. Hara M, Yaar M, Tang A, Eller MS, Reenstra W, Gilchrest BA. Role of integrins in melanocyte attachment and dendricity. J Cell Sci 1994;107(Pt 10):2739–2748.

    PubMed  CAS  Google Scholar 

  35. Neitmann M, Alexander M, Brinckmann J, Schlenke P, Tronnier M. Attachment and chemotaxis of melanocytes after ultraviolet irradiation in vitro. Br J Dermatol 1999;141:794–801.

    Article  PubMed  CAS  Google Scholar 

  36. Mengeaud V, Grob JJ, Bongrand P, et al. Adhesive and migratory behaviors of nevus cells differ from those of epidermal melanocytes and are not linked to the histological type of nevus. J Invest Dermatol 1996;106:1224–1229.

    Article  PubMed  CAS  Google Scholar 

  37. Bacharach-Buhles M, Lubowietzki M, Altmeyer P. Dose-dependent shift of apoptotic and unaltered melanocytes into the dermis after irradiation with UVA 1. Dermatology 1999;198:5–10.

    Article  PubMed  CAS  Google Scholar 

  38. Rodrigues GA, Park M. Oncogenic activation of tyrosine kinases. Curr Opin Genet Dev 1994;4:15–24.

    Article  PubMed  CAS  Google Scholar 

  39. Stove C, Stove V, Derycke L, Van Marck V, Mareel M, Bracke M. The heregulin/human epidermal growth factor receptor as a new growth factor system in melanoma with multiple ways of deregulation. J Invest Dermatol 2003;121:802–812.

    Article  PubMed  CAS  Google Scholar 

  40. Montone KT, van Belle P, Elenitsas R, Elder DE. Proto-oncogene c-kit expression in malignant melanoma: protein loss with tumor progression. Mod Pathol 1997;10:939–944.

    PubMed  CAS  Google Scholar 

  41. Baldi A, Santini D, Battista T, et al. Expression of AP-2 transcription factor and of its downstream target genes c-kit, E-cadherin and p21 in human cutaneous melanoma. J Cell Biochem 2001;83:364–372.

    Article  PubMed  CAS  Google Scholar 

  42. Huang S, Luca M, Gutman M, et al. Enforced c-KIT expression renders highly metastatic human melanoma cells susceptible to stem cell factor-induced apoptosis and inhibits their tumorigenic and metastatic potential. Oncogene 1996;13:2339–2347.

    PubMed  CAS  Google Scholar 

  43. Huang S, Jean D, Luca M, Tainsky MA, Bar-Eli M. Loss of AP-2 results in downregulation of c-KIT and enhancement of melanoma tumorigenicity and metastasis. Embo J 1998;17:4358–4369.

    Article  PubMed  CAS  Google Scholar 

  44. Wittbrodt J, Adam D, Malitschek B, et al. Novel putative receptor tyrosine kinase encoded by the melanoma-inducing Tu locus in Xiphophorus. Nature 1989;341:415–421.

    Article  PubMed  CAS  Google Scholar 

  45. Dimitrijevic N, Winkler C, Wellbrock C, et al. Activation of the Xmrk proto-oncogene of Xiphophorus by overexpression and mutational alterations. Oncogene 1998;16:1681–1690.

    Article  PubMed  CAS  Google Scholar 

  46. Gomez A, Wellbrock C, Gutbrod H, Dimitrijevic N, Schartl M. Ligand-independent dimerization and activation of the oncogenic xmrk receptor by two mutations in the extracellular domain. J Biol Chem 2001;276:3333–3340.

    Article  PubMed  CAS  Google Scholar 

  47. Palmer JS, Duffy DL, Box NF, et al. Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype? Am J Hum Genet 2000;66:176–186.

    Article  PubMed  CAS  Google Scholar 

  48. Scott MC, Wakamatsu K, Ito S, et al. Human melanocortin 1 receptor variants, receptor function and melanocyte response to UV radiation. J Cell Sci 2002;115:2349–2355.

    PubMed  CAS  Google Scholar 

  49. Seftor RE. Role of the beta3 integrin subunit in human primary melanoma progression: multifunctional activities associated with alpha(v)beta3 integrin expression. Am J Pathol 1998;153:1347–1351.

    PubMed  CAS  Google Scholar 

  50. Chang F, Steelman LS, Shelton JG, et al. Regulation of cell cycle progression and apoptosis by the Ras/Raf/MEK/ERK pathway (Review). Int J Oncol 2003;22:469–480.

    PubMed  CAS  Google Scholar 

  51. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949–954.

    Article  PubMed  CAS  Google Scholar 

  52. Satyamoorthy K, Li G, Gerrero MR, et al. Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res 2003;63:756–759.

    PubMed  CAS  Google Scholar 

  53. Kortylewski M, Heinrich PC, Kauffmann ME, Bohm M, MacKiewicz A, Behrmann I. Mitogenactivated protein kinases control p27/Kip1 expression and growth of human melanoma cells. Biochem J 2001;357:297–303.

    Article  PubMed  CAS  Google Scholar 

  54. Cohen C, Zavala-Pompa A, Sequeira JH, et al. Mitogen-activated protein kinase activation is an early event in melanoma progression. Clin Cancer Res 2002;8:3728–3733.

    PubMed  CAS  Google Scholar 

  55. Wellbrock C, Schartl M. Multiple binding sites in the growth factor receptor Xmrk mediate binding to p59fyn, GRB2 and Shc. Eur J Biochem 1999;260:275–283.

    Article  PubMed  CAS  Google Scholar 

  56. Wellbrock C, Ogilvie L, Hedley D, et al. V599EB-RAF is an Oncogene in Melanocytes. Cancer Res 2004;64:2338–2342.

    Article  PubMed  CAS  Google Scholar 

  57. Govindarajan B, Bai X, Cohen C, et al. Malignant transformation of melanocytes to melanoma by constitutive activation of mitogen-activated protein kinase kinase (MAPKK) signaling. J Biol Chem 2003;278:9790–9795.

    Article  PubMed  CAS  Google Scholar 

  58. Powell MB, Hyman P, Bell OD, et al. Hyperpigmentation and melanocytic hyperplasia in transgenic mice expressing the human T24 Ha-ras gene regulated by a mouse tyrosinase promoter. Mol Carcinog 1995;12:82–90.

    Article  PubMed  CAS  Google Scholar 

  59. Chin L, Pomerantz J, Polsky D, et al. Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Genes Dev 1997;11:2822–2834.

    PubMed  CAS  Google Scholar 

  60. Pollock PM, Harper UL, Hansen KS, et al. High frequency of BRAF mutations in nevi. Nat Genet 2003;33:19–20.

    Article  PubMed  CAS  Google Scholar 

  61. Busca R, Abbe P, Mantoux F, et al. Ras mediates the cAMP-dependent activation of extracellular signal-regulated kinases (ERKs) in melanocytes. Embo J 2000;19:2900–2910.

    Article  PubMed  CAS  Google Scholar 

  62. Bertolotto C, Busca R, Abbe P, et al. Different cis-acting elements are involved in the regulation of TRP1 and TRP2 promoter activities by cyclic AMP: pivotal role of M boxes (GTCATGTGCT) and of microphthalmia. Mol Cell Biol 1998;18:694–702.

    PubMed  CAS  Google Scholar 

  63. Wellbrock C, Weisser C, Geissinger E, Troppmair J, Schartl M. Activation of p59(Fyn) leads to melanocyte dedifferentiation by influencing MKP-1-regulated mitogen-activated protein kinase signaling. J Biol Chem 2002;277:6443–6454.

    Article  PubMed  CAS  Google Scholar 

  64. Englaro W, Bertolotto C, Busca R, et al. Inhibition of the mitogen-activated protein kinase pathway triggers B16 melanoma cell differentiation. J Biol Chem 1998;273:9966–9970.

    Article  PubMed  CAS  Google Scholar 

  65. Delfgaauw J, Duschl J, Wellbrock C, Froschauer C, Schartl M, Altschmied J. MITF-M plays an essential role in transcriptional activation and signal transduction in Xiphophorus melanoma. Gene 2003;320:117–126.

    Article  PubMed  CAS  Google Scholar 

  66. Goding CR. Mitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineage. Genes Dev 2000;14:1712–1728.

    PubMed  CAS  Google Scholar 

  67. Hemesath TJ, Price ER, Takemoto C, Badalian T, Fisher DE. MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes. Nature 1998;391:298–301.

    Article  PubMed  CAS  Google Scholar 

  68. Wu M, Hemesath TJ, Takemoto CM, et al. c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi. Genes Dev 2000;14:301–312.

    PubMed  CAS  Google Scholar 

  69. Xu W, Gong L, Haddad MM, et al. Regulation of microphthalmia-associated transcription factor MITF protein levels by association with the ubiquitin-conjugating enzyme hUBC9. Exp Cell Res 2000;255:135–143.

    Article  PubMed  CAS  Google Scholar 

  70. Price ER, Ding HF, Badalian T, et al. Lineage-specific signaling in melanocytes. C-kit stimulation recruits p300/CBP to microphthalmia. J Biol Chem 1998;273:17,983–17,986.

    Article  PubMed  CAS  Google Scholar 

  71. King R, Weilbaecher KN, McGill G, Cooley E, Mihm M, Fisher DE. Microphthalmia transcription factor. A sensitive and specific melanocyte marker for Melanoma Diagnosis. Am J Pathol 1999;155:731–738.

    PubMed  CAS  Google Scholar 

  72. Selzer E, Wacheck V, Lucas T, et al. The melanocyte-specific isoform of the microphthalmia transcription factor affects the phenotype of human melanoma. Cancer Res 2002;62:2098–2103.

    PubMed  CAS  Google Scholar 

  73. Widlund HR, Horstmann MA, Price ER, et al. Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor. J Cell Biol 2002;158:1079–1087.

    Article  PubMed  CAS  Google Scholar 

  74. McGill GG, Horstmann M, Widlund HR, et al. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. Cell 2002;109:707–718.

    Article  PubMed  CAS  Google Scholar 

  75. Eisen T, Easty DJ, Bennett DC, Goding CR. The POU domain transcription factor Brn-2: elevated expression in malignant melanoma and regulation of melanocyte-specific gene expression. Oncogene 1995;11:2157–2164.

    PubMed  CAS  Google Scholar 

  76. Thomson JA, Murphy K, Baker E, et al. The brn-2 gene regulates the melanocytic phenotype and tumorigenic potential of human melanoma cells. Oncogene 1995;11:691–700.

    PubMed  CAS  Google Scholar 

  77. Goodall J, Wellbrock C, Dexter TJ, Roberts K, Marais R, Goding CR. The Brn-2 transcription factor links activated BRAF to melanoma proliferation. Mol Cell Biol 2004;24:2923–2931.

    Article  PubMed  CAS  Google Scholar 

  78. Goodall J, Martinozzi S, Dexter TJ, et al. Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin. Mol Cell Biol 2004;24:2915–2922.

    Article  PubMed  CAS  Google Scholar 

  79. Cook AL, Donatien PD, Smith AG, et al. Human melanoblasts in culture: expression of BRN2 and synergistic regulation by fibroblast growth factor-2, stem cell factor, and endothelin-3. J Invest Dermatol 2003;121:1150–1159.

    Article  PubMed  CAS  Google Scholar 

  80. Philip S, Bulbule A, Kundu GC. Osteopontin stimulates tumor growth and activation of promatrix metalloproteinase-2 through nuclear factor-kappa B-mediated induction of membrane type 1 matrix metalloproteinase in murine melanoma cells. J Biol Chem 2001;276:44,926–44,935.

    Article  PubMed  CAS  Google Scholar 

  81. Nemoto H, Rittling SR, Yoshitake H, et al. Osteopontin deficiency reduces experimental tumor cell metastasis to bone and soft tissues. J Bone Miner Res 2001;16:652–659.

    Article  PubMed  CAS  Google Scholar 

  82. Geissinger E, Weisser C, Fischer P, Schartl M, Wellbrock C. Autocrine stimulation by osteopontin contributes to antiapoptotic signalling of melanocytes in dermal collagen. Cancer Res 2002;62:4820–4828.

    PubMed  CAS  Google Scholar 

  83. Petitclerc E, Stromblad S, von Schalscha TL, et al. Integrin alpha(v)beta3 promotes M21 melanoma growth in human skin by regulating tumor cell survival. Cancer Res 1999;59:2724–2730.

    PubMed  CAS  Google Scholar 

  84. Abram CL, Courtneidge SA. Src family tyrosine kinases and growth factor signaling. Exp Cell Res 2000;254:1–13.

    Article  PubMed  CAS  Google Scholar 

  85. Schartl M, Barnekow A, Bauer H, Anders F. Correlations of inheritance and expression between a tumor gene and the cellular homolog of the Rous sarcoma virus-transforming gene in Xiphophorus. Cancer Res 1982;42:4222–4227.

    PubMed  CAS  Google Scholar 

  86. Yayon A, Ma YS, Safran M, Klagsbrun M, Halaban R. Suppression of autocrine cell proliferation and tumorigenesis of human melanoma cells and fibroblast growth factor transformed fibroblasts by a kinase-deficient FGF receptor 1: evidence for the involvement of Src-family kinases. Oncogene 1997;14:2999–3009.

    Article  PubMed  CAS  Google Scholar 

  87. Wellbrock C, Gomez A, Schartl M. Signal transduction by the oncogenic receptor tyrosine kinase Xmrk in melanoma formation of Xiphophorus. Pigment Cell Res 1997;10:34–40.

    Article  PubMed  CAS  Google Scholar 

  88. Loganzo F, Dosik JS, Zhao Y, et al. Elevated expression of protein tyrosine kinase c-Yes, but not c-Src, in human malignant melanoma. Oncogene 1993;8:2637–2644.

    PubMed  CAS  Google Scholar 

  89. Marchetti D, Parikh N, Sudol M, Gallick GE. Stimulation of the protein tyrosine kinase c-Yes but not c-Src by neurotrophins in human brain-metastatic melanoma cells. Oncogene 1998;16:3253–3260.

    Article  PubMed  CAS  Google Scholar 

  90. Wellbrock C, Lammers R, Ullrich A, Schartl M. Association between the melanoma-inducing receptor tyrosine kinase Xmrk and src family tyrosine kinases in Xiphophorus. Oncogene 1995;10:2135–2143.

    PubMed  CAS  Google Scholar 

  91. Wellbrock C, Schartl M. Activation of phosphatidylinositol 3-kinase by a complex of p59fyn and the receptor tyrosine kinase Xmrk is involved in malignant transformation of pigment cells. Eur J Biochem 2000;267:3513–3522.

    Article  PubMed  CAS  Google Scholar 

  92. Huang J, Asawa T, Takato T, Sakai R. Cooperative roles of Fyn and cortactin in cell migration of metastatic murine melanoma. J Biol Chem 2003;278:48,367–48,376.

    Article  PubMed  CAS  Google Scholar 

  93. Fukui Y, Ihara S, Nagata S. Downstream of phosphatidylinositol-3 kinase, a multifunctional signaling molecule, and its regulation in cell responses. J Biochem (Tokyo) 1998;124:1–7.

    CAS  Google Scholar 

  94. Wu H, Goel V, Haluska FG. PTEN signaling pathways in melanoma. Oncogene 2003;22:3113–3122.

    Article  PubMed  CAS  Google Scholar 

  95. Tsao H, Zhang X, Fowlkes K, Haluska FG. Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma cell lines. Cancer Res 2000;60:1800–1804.

    PubMed  CAS  Google Scholar 

  96. Tsao H, Goel V, Wu H, Yang G, Haluska FG. Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma. J Invest Dermatol 2004;122:337–341.

    Article  PubMed  CAS  Google Scholar 

  97. Chen H, Salopek TG, Jimbow K. The role of phosphoinositide 3-kinase in the sorting and transport of newly synthesized tyrosinase-related protein-1 (TRP-1). J Investig Dermatol Symp Proc 2001;6:105–114.

    Article  PubMed  CAS  Google Scholar 

  98. Li G, Schaider H, Satyamoorthy K, Hanakawa Y, Hashimoto K, Herlyn M. Downregulation of E-cadherin and Desmoglein 1 by autocrine hepatocyte growth factor during melanoma development. Oncogene 2001;20:8125–8135.

    Article  PubMed  CAS  Google Scholar 

  99. Hodgson L, Henderson AJ, Dong C. Melanoma cell migration to type IV collagen requires activation of NF-kappaB. Oncogene 2003;22:98–108.

    Article  PubMed  CAS  Google Scholar 

  100. Li G, Satyamoorthy K, Herlyn M. N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells. Cancer Res 2001;61:3819–3825.

    PubMed  CAS  Google Scholar 

  101. Busca R, Bertolotto C, Ortonne JP, Ballotti R. Inhibition of the phosphatidylinositol 3-kinase/p70(S6)-kinase pathway induces B16 melanoma cell differentiation. J Biol Chem 1996;271:31,824–31,830.

    Article  PubMed  CAS  Google Scholar 

  102. Takeda K, Takemoto C, Kobayashi I, et al. Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a phosphorylation site with functional significance. Hum Mol Genet 2000;9:125–132.

    Article  PubMed  CAS  Google Scholar 

  103. Khaled M, Larribere L, Bille K, et al. Glycogen synthase kinase 3beta is activated by cAMP and plays an active role in the regulation of melanogenesis. J Biol Chem 2002;277:33,690–33,697.

    Article  PubMed  CAS  Google Scholar 

  104. Khaled M, Larribere L, Bille K, Ortonne JP, Ballotti R, Bertolotto C. Microphthalmia associated transcription factor is a target of the phosphatidylinositol-3-kinase pathway. J Invest Dermatol 2003;121:831–836.

    Article  PubMed  CAS  Google Scholar 

  105. Dhawan P, Singh AB, Ellis DL, Richmond A. Constitutive activation of Akt/protein kinase B in melanoma leads to up-regulation of nuclear factor-kappaB and tumor progression. Cancer Res 2002;62:7335–7342.

    PubMed  CAS  Google Scholar 

  106. Wellbrock C, Fischer P, Schartl M. PI3-kinase is involved in mitogenic signaling by the oncogenic receptor tyrosine kinase Xiphophorus melanoma receptor kinase in fish melanoma. Exp Cell Res 1999;251:340–349.

    Article  PubMed  CAS  Google Scholar 

  107. Stewart AL, Mhashilkar AM, Yang XH, et al. PI3 kinase blockade by Ad-PTEN inhibits invasion and induces apoptosis in RGP and metastatic melanoma cells. Mol Med 2002;8:451–461.

    PubMed  CAS  Google Scholar 

  108. Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C. PI3K/Akt and apoptosis: size matters. Oncogene 2003;22:8983–8998.

    Article  PubMed  CAS  Google Scholar 

  109. Stahl JM, Cheung M, Sharma A, Trivedi NR, Shanmugam S, Robertson GP. Loss of PTEN promotes tumor development in malignant melanoma. Cancer Res 2003;63:2881–2890.

    PubMed  CAS  Google Scholar 

  110. Ivanov VN, Hei TK. Arsenite treatment sensitizes human melanomas to apoptosis via TNF-mediated pathway. J Biol Chem 2004;279:22,747–22,758.

    Article  PubMed  CAS  Google Scholar 

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  1. Signal Transduction Team, Cell and Molecular Biology Section, The Institute of Cancer Research, London, UK

    Claudia Wellbrock

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  1. Claudia Wellbrock
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Editors and Affiliations

  1. Laboratory of Cell Biology National Cancer Institute, National Institutes of Health, Bethesda, MD

    Vincent J. Hearing PhD

  2. Department of Surgery, University of California, San Francisco

    Stanley P. L. Leong MD

  3. School of Medicine, San Francisco, CA

    Stanley P. L. Leong MD

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© 2006 Humana Press Inc., Totowa, N.J.

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Wellbrock, C. (2006). Melanoma Development and Pigment Cell Transformation. In: Hearing, V.J., Leong, S.P.L. (eds) From Melanocytes to Melanoma. Humana Press. https://doi.org/10.1007/978-1-59259-994-3_14

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  • DOI: https://doi.org/10.1007/978-1-59259-994-3_14

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-459-3

  • Online ISBN: 978-1-59259-994-3

  • eBook Packages: MedicineMedicine (R0)

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