Association of MITF and other melanosome-related proteins with chemoresistance in melanoma tumors and cell lines.
Melanoma Res
; 23(5): 360-5, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23921446
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Biomarcadores Tumorais
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Resistencia a Medicamentos Antineoplásicos
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Melanossomas
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Fator de Transcrição Associado à Microftalmia
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Melanoma
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Antineoplásicos
Tipo de estudo:
Risk_factors_studies
Limite:
Aged80
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article