Association of MITF and other melanosome-related proteins with chemoresistance in melanoma tumors and cell lines

作者：Johansson Carolina Hertzman^*; Azimi Alireza; Stolt Marianne Frostvik; Shojaee Seyedmehdi; Wiberg Henning; Grafstrom Eva; Hansson Johan; Brage Suzanne Egyhazi

来源：Melanoma Research, 2013, 23(5): 360-365.

DOI：10.1097/CMR.0b013e328362f9cd

• chemotherapy resistance
• dacarbazine
• gp100/PMEL
• GPR143
• melanogenesis
• melanoma
• melanosomes
• MITF
• temozolomide

Previous studies in cell lines have suggested a role for melanosomes and related protein trafficking pathways in melanoma drug response. We have investigated the expression of six proteins related to melanosomes and melanogenesis (MITF, GPR143, gp100/PMEL, MLANA, TYRP1, and RAB27A) in pretreatment metastases from melanoma patients (n=52) with different response to dacarbazine/temozolomide. Microphthalmia-associated transcription factor (MITF) and G-protein coupled receptor 143 (GPR143) showed significantly higher expression in nonresponders compared with responders. The premelanosome protein (gp100/PMEL) has been indicated previously in resistance to cisplatin in melanoma cells, but the expression levels of gp100/PMEL showed no association with response to dacarbazine/temozolomide in our clinical material. We also investigated the effects on chemosensitivity of siRNA inhibition of gp100/PMEL in the MNT-1 melanoma cell line. As expected from the study of the tumor material, no effect was detected with respect to response to temozolomide. However, knockdown of gp100/PMEL sensitized the cells to both paclitaxel and cisplatin. Overall, our results suggest that MITF, and several MITF-regulated factors, are associated with resistance to chemotherapy in melanoma and that different MITF targets can be of importance for different drugs.

• 出版日期2013-10