Pak B J, Li Q, Kerbel R S, Ben-David Y
Sunnybrook and Women's College Health Sciences Centre and Toronto Sunnybrook Regional Cancer Centre, Division of Cancer Biology Research, Ontario, Canada.
Melanoma Res. 2000 Oct;10(5):499-505. doi: 10.1097/00008390-200010000-00013.
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.
酪氨酸酶相关蛋白2（TYRP2）是一种黑素细胞特异性酶，在黑色素生物合成途径中催化L - 多巴色素的非脱羧互变异构反应生成5,6 - 二羟基吲哚 - 2 - 羧酸（DHICA）。我们最近证明，人黑色素瘤细胞中TYRP2的组成型表达与顺二氯二氨铂（II）（CDDP）耐药性呈正相关，并且在对CDDP敏感的细胞中异位表达TYRP2会使它们对CDDP治疗更具抗性。在此，我们证明组成型TYRP2表达与CDDP耐药性之间的这种相关性适用于从处于疾病进展不同阶段的黑色素瘤患者获得的一组不同的人黑色素瘤细胞系。我们进一步表明，CDDP耐药性仅与TYRP2表达相关，与酪氨酸酶和TYRP1表达以及细胞黑色素含量均无关。总之，这些结果进一步支持了TYRP2是黑色素瘤细胞中CDDP耐药性的新型介质这一观点，并表明TYRP2的这一功能独立于细胞黑色素含量和黑色素生成途径的其他调节酶。
