Short ReportTYRP2-mediated resistance to cis-diamminedichloroplatinum (II) in human melanoma cells is independent of tyrosinase and TYRP1 expression and melanin contentPak, B. J.; Li, Q.; Kerbel, R. S.; Ben-David, Y.*Author Information Sunnybrook and Women's College Health Sciences Centre and Toronto Sunnybrook Regional Cancer Centre, Division of Cancer Biology Research, Research Building, Room S-218, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5. Tel: (+1) 416 480 6100 ext. 3351; Fax: (+1) 416 480 5703; Email: [email protected] (B. J. Pak, Q. Li, R. S. Kerbel, Y. Ben-David). Department of Medical Biophysics, University of Toronto, Canada (R. S. Kerbel, Y. Ben-David). *To whom correspondence should be addressed (Received 19 April 2000; accepted in revised form 17 July 2000 Melanoma Research: October 2000 - Volume 10 - Issue 5 - p 499-505 Buy 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. © 2000 Lippincott Williams & Wilkins, Inc.