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

Hertzman Johansson, Carolina; Azimi, Alireza; Frostvik Stolt, Marianne; Shojaee, Seyedmehdi; Wiberg, Henning; Grafström, Eva; Hansson, Johan; Egyházi Brage, Suzanne

doi: 10.1097/CMR.0b013e328362f9cd
ORIGINAL ARTICLES: Translational research

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.

Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

All supplementary digital content is available directly from the corresponding author.

Correspondence to Carolina Hertzman Johansson, PhD, Department of Oncology-Pathology, Karolinska Institutet, CCK R8:03, Karolinska University Hospital, Solna, S-17176 Stockholm, Sweden Tel: +46 8 51776313; fax: +46 8 318327; e-mail: carolina.johansson@ki.se

Received December 6, 2012

Accepted April 19, 2013

© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins