title: TYRP2-mediated resistance to cis-diamminedichloroplatinum (II) in human melanoma cells is independent of tyrosinase and TYRP1 expression and melanin content.
abstract: Tyrosinase-related protein-2 (TYRP2) is a melanocyte-specific enzyme that catalyses the non-decarboxylative tautomerization of L-dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in the melanin biosynthetic pathway. We have recently demonstrated that the constitutive expression of TYRP2 in human melanoma cells positively correlates with cis-diamminedichloroplatinum (II) (CDDP) resistance, and that the ectopic expression of TYRP2 in CDDP-sensitive cells rendered them more resistant to CDDP treatment. Here, we demonstrate that this correlation between constitutive TYRP2 expression and CDDP resistance applies to a panel of distinct human melanoma cell lines obtained from patients with melanoma at various stages of disease progression. We further show that CDDP resistance correlates only with TYRP2 expression and is associated neither with tyrosinase and TYRP1 expression, nor with cellular melanin content. Together, these results further support the notion that TYRP2 is a novel mediator of CDDP resistance in melanoma cells and suggest that this function of TYRP2 is independent of cellular melanin content and of the other regulatory enzymes of the melanogenic pathway.
authors.affiliation: Sunnybrook and Women's College Health Sciences Centre and Toronto Sunnybrook Regional Cancer Centre, Division of Cancer Biology Research, Ontario, Canada.
authors.forename: B J
authors.initials: BJ
authors.lastname: Pak
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: R S
authors.initials: RS
authors.lastname: Kerbel
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-David
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D019008:Drug Resistance, Neoplasm; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma; D008562:Membrane Glycoproteins; D014442:Monophenol Monooxygenase / Q000235:genetics; D010088:Oxidoreductases; D011506:Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D008543:Melanins; D008562:Membrane Glycoproteins; D011506:Proteins; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; D002945:Cisplatin