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Lineage-specific Mechanism of Drug and Radiation Resistance in Melanoma Mediated by Tyrosinase-related Protein 2

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Abstract

A major obstacle in the clinical management of malignant melanoma is its intrinsic resistance to chemotherapy and radiation therapy. Consequently, most patients with melanoma often do not respond to conventional anticancer therapy in a clinically significant manner. Recent advances in cancer research have provided new insights into the mechanisms of intrinsic resistance in melanomas. We have recently reported that the over-expression of tyrosinase-related protein 2 (TYRP2), an enzyme that is well characterized for its function in melanin synthesis, is associated specifically with resistance to DNA damaging drugs and radiation treatment. This review will summarize our findings as well as discuss the possible mechanisms by which TYRP2 over-expression contributes to intrinsic resistance in human malignant melanoma.

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References

  1. Volkenandt M,Schlegel U,Nanus DM,Albino AP: Mutational analysis of the human p53 gene in malignant melanoma. Pigment Cell Res 4: 35–40, 1991

    Google Scholar 

  2. Castresana JS,Rubio MP,Vazquez JJ,Idoate M,Sober AJ,Seizinger BR,Barnhill RL: Lack of allelic deletion and point mutation as mechanisms of p53 activation in human malignant melanoma. Int J Cancer 55: 562–565, 1993

    Google Scholar 

  3. Weiss J,Schwechheimer K,Cavenee WK,Herlyn M,Arden KC: Mutation and expression of the p53 gene in malignant melanoma cell lines. Int J Cancer 54: 693–699, 1993

    Google Scholar 

  4. Weiss J,Heine M,Korner B,Pilch H,Jung EG: Expression of p53 protein in malignant melanoma: clinicopathological and prognostic implications. Br J Dermatol 133: 23–31, 1995

    Google Scholar 

  5. Albino AP,Vidal MJ,McNutt NS,Shea CR,Prieto VG,Nanus DM,Palmer JM,Hayward NK: Mutation and expression of the p53 gene in human malignant melanoma. Melanoma Res 4: 35–45, 1994

    Google Scholar 

  6. Florenes VA,Oyjord T,Holm R,Skrede M,Borresen AL,Nesland JM,Fodstad O: TP53 allele loss, mutations and expression in malignant melanoma. Br J Cancer 69: 253–259, 1994

    Google Scholar 

  7. Lubbe J,Reichel M,Burg G,Kleihues P: Absence of p53 gene mutations in cutaneous melanoma. J Invest Dermatol 102: 819–821, 1994

    Google Scholar 

  8. Montano X,Shamsher M,Whitehead P,Dawson K,Newton J: Analysis of p53 in human cutaneous melanoma cell lines. Oncogene 9: 1455–1459, 1994

    Google Scholar 

  9. Plettenberg A,Ballaun C,Pammer J,Mildner M,Strunk D,Weninger W,Tschachler E: Human melanocytes and melanoma cells constitutively express the Bcl-2 protooncogene in situ and in cell culture. Am J Pathol 146: 651–659, 1995

    Google Scholar 

  10. Cerroni L,Soyer HP,Kerl H: bcl-2 protein expression in cutaneous malignant melanoma and benign melanocytic nevi. Am J Dermatopathol 17: 7–11, 1995

    Google Scholar 

  11. Morales-Ducret CR,van de Rijn M,LeBrun DP,Smoller BR: bcl-2 expression in primary malignancies of the skin. Arch Dermatol 131: 909–912, 1995

    Google Scholar 

  12. Tron VA,Krajewski S,Klein-Parker H,Li G,Ho VC,Reed JC: Immunohistochemical analysis of Bcl-2 protein regulation in cutaneous melanoma. Am J Pathol 146: 643–650, 1995

    Google Scholar 

  13. Grover R,Wilson GD: Bcl-2 expression in malignant melanoma and its prognostic significance. Eur J Surg Oncol 22: 347–349, 1996

    Google Scholar 

  14. Jansen B,Schlagbauer-Wadl H,Brown BD,Bryan RN,van Elsas A,Muller M,Wolff K,Eichler HG,Pehamberger H: bcl-2 antisense therapy chemosensitizes human melanoma in SCID mice. Nat Med 4: 232–234, 1998

    Google Scholar 

  15. Leiter U,Schmid RM,Kaskel P,Peter RU,Krahn G: Antiapoptotic bcl-2 and bcl-xL in advanced malignant melanoma. Arch Dermatol Res 292: 225–232, 2000

    Google Scholar 

  16. Tang L,Tron VA,Reed JC,Mah KJ,Krajewska M,Li G,Zhou X,Ho VC,Trotter MJ: Expression of apoptosis regulators in cutaneous malignant melanoma. Clin Cancer Res 4: 1865–1871, 1998

    Google Scholar 

  17. Selzer E,Schlagbauer-Wadl H,Okamoto I,Pehamberger H,Potter R,Jansen B: Expression of Bcl-2 family members in human melanocytes, in melanoma metastases and in melanoma cell lines. Melanoma Res 8: 197–203, 1998

    Google Scholar 

  18. Grossman D,McNiff JM,Li F,Altieri DC: Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma. J Invest Dermatol 113: 1076–1081, 1999

    Google Scholar 

  19. Goldstein LJ,Galski H,Fojo A,Willingham M,Lai SL,Gazdar A,Pirker R,Green A,Crist W,Brodeur GM: Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 81: 116–124, 1989

    Google Scholar 

  20. Tsuruo T,Sugimoto Y,Hamada H,Roninson I,Okumura M,Adachi K,Morishima Y,Ohno R: Detection of multidrug resistance markers, P-glycoprotein and mdr1 mRNA, in human leukemia cells. Jpn J Cancer Res 78: 1415–1419, 1987

    Google Scholar 

  21. Fuqua SA,Moretti-Rojas IM,Schneider SL,McGuire WL: P-glycoprotein expression in human breast cancer cells. Cancer Res 47: 2103–2106, 1987

    Google Scholar 

  22. Nabors MW,Griffin CA,Zehnbauer BA,Hruban RH,Phillips PC,Grossman SA,Brem H,Colvin OM: Multidrug resistance gene (MDR1) expression in human brain tumors. J Neurosurg 75: 941–946, 1991

    Google Scholar 

  23. van der V,van Kalken CK,Ketelaars H,Broxterman HJ,Scheffer G,Kuiper CM,Tsuruo T,Lankelma J,Meijer CJ,Pinedo HM: Distribution of multi-drug resistance-associated P-glycoprotein in normal and neoplastic human tissues. Analysis with 3 monoclonal antibodies recognizing different epitopes of the P-glycoprotein molecule. Ann Oncol 1: 56–64, 1990

    Google Scholar 

  24. Batist G,Torres-Garcia S,Demuys JM,Greene D,Lehnert S,Rochon M,Panasci L: Enhanced DNA cross-link removal: the apparent mechanism of resistance in a clinically relevant melphalan-resistant human breast cancer cell line. Mol Pharmacol 36: 224-230, 1989

    Google Scholar 

  25. Britten RA,Liu D,Tessier A,Hutchison MJ,Murray D: ERCC1 expression as a molecular marker of cisplatin resistance in human cervical tumor cells. Int J Cancer 89: 453–457, 2000

    Google Scholar 

  26. Ferry KV,Hamilton TC,Johnson SW: Increased nucleotide excision repair in cisplatin-resistant ovarian cancer cells. Role Of ercc1-xpf (In Process Citation). Biochem Pharmacol 60: 1305–1313, 2000

    Google Scholar 

  27. Lu SJ,Man S,Bani MR,Adachi D,Hawley RG,Kerbel RS,Ben-David Y: Retroviral insertional mutagenesis as a strategy for the identification of genes associated with cisdiamminedichloroplatinum( II) resistance. Cancer Res 55: 1139–1145, 1995

    Google Scholar 

  28. Chu W,Pak BJ,Bani MR,Kapoor M,Lu SJ,Tamir A,Kerbel RS,Ben-David Y: Tyrosinase-related protein 2 as a mediator of melanoma specific resistance to cisdiamminedichloroplatinum( II): therapeutic implications. Oncogene 19: 395–402, 2000

    Google Scholar 

  29. Chu G: Cellular responses to cisplatin. The roles of DNAbinding proteins and DNA repair. J Biol Chem 269: 787–790, 1994

    Google Scholar 

  30. Pak BJ,Li Q,Kerbel RS,Ben-David Y: TYRP2-mediated resistance to cis-diamminedichloroplatinum (II) in human melanoma cells is independent of tyrosinase and TYRP1 expression and melanin content (In Process Citation). Melanoma Res 10: 499–505, 2000

    Google Scholar 

  31. Riley PA: Melanin. Int J Biochem Cell Biol 29: 1235–1239, 1997

    Google Scholar 

  32. Hearing VJ,Tsukamoto K: Enzymatic control of pigmentation in mammals. FASEB J 5: 2902–2909, 1991

    Google Scholar 

  33. Tripathi RK,Hearing VJ,Urabe K,Aroca P,Spritz RA: Mutational mapping of the catalytic activities of human tyrosinase. J Biol Chem 267: 23707–23712, 1992

    Google Scholar 

  34. Jimenez-Cervantes C,Solano F,Kobayashi T,Urabe K,Hearing VJ,Lozano JA,Garcia-Borron JC: A new enzymatic function in the melanogenic pathway. The 5,6-dihydroxyindole-2-carboxylic acid oxidase activity of tyrosinase-related protein-1 (TRP1). J Biol Chem 269: 17993–18000, 1994

    Google Scholar 

  35. Kobayashi T,Urabe K,Winder A,Jimenez-Cervantes C,Imokawa G,Brewington T,Solano F,Garcia-Borron JC,Hearing VJ: Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis. EMBO J 13: 5818–5825, 1994

    Google Scholar 

  36. Boissy RE,Sakai C,Zhao H,Kobayashi T,Hearing VJ: Human tyrosinase related protein-1 (TRP-1) does not function as a DHICA oxidase activity in contrast to murine TRP-1. Exp Dermatol 7: 198–204, 1998

    Google Scholar 

  37. Tsukamoto K,Jackson IJ,Urabe K,Montague PM,Hearing VJ: A second tyrosinase-related protein, TRP-2, is a melanogenic enzyme termed DOPAchrome tautomerase. EMBO J 11: 519–526, 1992

    Google Scholar 

  38. Leonard LJ,Townsend D,King RA: Function of dopachrome oxidoreductase and metal ions in dopachrome conversion in the eumelanin pathway. Biochemistry 27: 6156–6159, 1988

    Google Scholar 

  39. Kroumpouzos G,Urabe K,Kobayashi T,Sakai C,Hearing VJ: Functional analysis of the slaty gene product (TRP2) as dopachrome tautomerase and the effect of a point mutation on its catalytic function. Biochem Biophys Res Commun 202: 1060–1068, 1994

    Google Scholar 

  40. Udono T,Takahashi K,Yasumoto K,Yoshizawa M,Takeda K,Abe T,Tamai M,Shibahara S: Expression of tyrosinase-related protein 2/DOPAchrome tautomerase in the retinoblastoma. Exp Eye Res 72: 225–234, 2001

    Google Scholar 

  41. Chi DD,Merchant RE,Rand R,Conrad AJ,Garrison D,Turner R,Morton DL,Hoon DS: Molecular detection of tumor-associated antigens shared by human cutaneous melanomas and gliomas. Am J Pathol 150: 2143–2152, 1997

    Google Scholar 

  42. Suzuki H,Takahashi K,Yasumoto K,Amae S,Yoshizawa M,Fuse N,Shibahara S: Role of neurofibrom in in modulation of expression of the tyrosinase-related protein 2 gene. J Biochem (Tokyo) 124: 992–998, 1998

    Google Scholar 

  43. Orlow SJ,Hearing VJ,Sakai C,Urabe K,Zhou BK,Silvers WK,Mintz B: Changes in expression of putative antigens encoded by pigment genes in mouse melanomas at different stages of malignant progression. Proc Natl Acad Sci USA 92: 10152–10156, 1995

    Google Scholar 

  44. Tuting T,Steitz J,Bruck J,Gambotto A,Steinbrink K,DeLeo AB,Robbins P,Knop J,Enk AH: Dendritic cell-based genetic immunization in mice with a recombinant adenovirus encoding murine TRP2 induces effective anti-melanoma immunity. J Gene Med 1: 400–406, 1999

    Google Scholar 

  45. Parkhurst MR,Fitzgerald EB,Southwood S,Sette A,Rosenberg SA,Kawakami Y: Identification of a shared HLA-A0201-restricted T-cell epitope from the melanoma antigen tyrosinase-related protein 2 (TRP2). Cancer Res 58: 4895–4901, 1998

    Google Scholar 

  46. Bloom MB,Perry-Lalley D,Robbins PF,Li Y,el-Gamil M,Rosenberg SA,Yang JC: Identification of tyrosinase-related prote in 2 as a tumor rejection antigen for the B16 melanoma. J Exp Med 185: 453–459, 1997

    Google Scholar 

  47. Nishioka E,Funasaka Y,Kondoh H,Chakraborty AK,Mishima Y,Ichihashi M: Expression of tyrosinase, TRP-1 and TRP-2 in ultraviolet-irradiated human melanomas and melanocytes: TRP-2 protects melanoma cells from ultraviolet B induced apoptosis. Melanoma Res 9: 433–443, 1999

    Google Scholar 

  48. Novellino L,Napolitano A,Prota G: 5,6-Dihydroxyindoles in the fenton reaction: a model study of the role of melanin precursors in oxidative stress and hyperpigmentary processes. Chem Res Toxicol 12: 985-992, 1999

    Google Scholar 

  49. Memoli S,Napolitano A,d'Ischia M,Misuraca G,Palumbo A,Prota G: Diffusible melanin-related metabolites are potent inhibitors of lipid peroxidation. Biochim Biophys Acta 1346: 61–68, 1997

    Google Scholar 

  50. Ivanov VN,Ronai Z: p38 protects human melanoma cells from UV-induced apoptosis through down-regulation of NF-kappaB activity and Fas expression. Oncogene 19: 3003–3012, 2000

    Google Scholar 

  51. Ivanov VN,Fodstad O,Ronai Z: Expression of ring fingerdeleted TRAF2 sensitizes metastatic melanoma cells to apoptosis via up-regulation of p38, TNFalpha and suppression of NF-kappaB activities. Oncogene 20: 2243–2253, 2001

    Google Scholar 

  52. Bhoumik A,Ivanov V,Ronai Z: Activating transcription factor 2-derived peptides alter resistance of human tumor cell lines to ultraviolet irradiation and chemical treatment. Clin Cancer Res 7: 331–342, 2001

    Google Scholar 

  53. Ivanov VN,Ronai Z: Down-regulation of tumor necrosis factor alpha expression by activating transcription factor 2 increases UVC-induced apoptosis of late-stage melanoma cells. J Biol Chem 274: 14079–14089, 1999

    Google Scholar 

  54. Franco AV,Zhang XD,Van Berkel E,Sanders JE,Zhang XY,Thomas WD,Nguyen T,Hersey P: The role of nf-kappab in tnf-related apoptosis-inducing ligand (trail)-induced apoptosis of melanoma cells. J Immunol 166: 5337–5345, 2001

    Google Scholar 

  55. Fokstuen T,Rabo YB,Zhou JN,Karlson J,Platz A,Shoshan MC,Hansson J,Linder S: The Ras farnesylation inhibitor BZA-5B increases the resistance to cisplatin in a human melanoma cell line. Anticancer Res 17: 2347–2352, 1997

    Google Scholar 

  56. Fang D,Kute T,Setaluri V: Regulation of tyrosinase-related protein-2 (TYRP2) in human melanocytes: relationship to growth and morphology. Pigment Cell Res 14: 132–139, 2001

    Google Scholar 

  57. Park KC,Kim DS,Choi HO,Kim KH,Chung JH,Eun HC,Lee JS,Seo JS: Overexpression of HSP70 prevents ultraviolet B-induced apoptosis of a human melanoma cell line. Arch Dermatol Res 292: 482-487, 2000

    Google Scholar 

  58. Wachsberger PR,Landry J,Storck C,Davis K,O'Hara MD,Owen CS,Leeper DB,Coss RA: Mammalian cells adapted to growth at pH 6.7 have elevated HSP27 levels and are resistant to cisplatin. Int J Hyperthermia 13: 251–255, 1997

    Google Scholar 

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Authors and Affiliations

  1. Molecular and Cellular Biology, Sunnybrook and Women's College Health Sciences Centre and Toronto Sunnybrook Regional Cancer Centre, Toronto

    Brian J. Pak, Wendy Chu, Shi Jiang Lu, Robert S. Kerbel & Yaacov Ben-David

  2. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    Wendy Chu, Robert S. Kerbel & Yaacov Ben-David

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  1. Brian J. Pak
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  2. Wendy Chu
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  3. Shi Jiang Lu
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  4. Robert S. Kerbel
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  5. Yaacov Ben-David
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Pak, B.J., Chu, W., Jiang Lu, S. et al. Lineage-specific Mechanism of Drug and Radiation Resistance in Melanoma Mediated by Tyrosinase-related Protein 2. Cancer Metastasis Rev 20, 27–32 (2001). https://doi.org/10.1023/A:1013175516793

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