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Int J Biol Macromol. 2015 Aug;79:44-8. doi: 10.1016/j.ijbiomac.2015.04.029. Epub 2015 Apr 23.

Protein disulfide isomerases: Impact of thapsigargin treatment on their expression in melanoma cell lines.

Author information

1
CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade Ciências Médicas da Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal.
2
CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade Ciências Médicas da Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal; Departamentio das Ciências da Vida, Faculdade de Ciências e Tecnologia da Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal.
3
CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade Ciências Médicas da Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal; UEI Parasitologia Médica, Instituto de Higiene e Medicina Tropical da Universidade NOVA de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal. Electronic address: cnovo@ihmt.unl.pt.

Abstract

Anti-cancer treatments usually elevate the content of unfolded or misfolded proteins in the endoplasmic reticulum (ER). Here we aimed to get insights into the relation between sensitivity of melanoma cell lines to the ER stress inducer thapsigargin (THG) and the genetic expression of protein disulfide isomerase family members (PDIs). The expression of PDIs was analysed by flow cytometry and real-time PCR. The results showed that SK-MEL-30, the less THG sensitive cell line, displays higher basal PDIs' expression levels and the sensitivity is increased by the PDIs inhibitor bacitracin. While SK-MEL-30 PDIs' expression is not THG dose-dependent, an increase in glucose related protein 78 (GRP78), PDIA5, PDIA6, and thioredoxin-related-transmembrane proteins' (TMX3 and TMX4) expression, in response to higher drug concentrations, was observed in MNT-1. The differences in PDIs' gene expression in MNT-1 suggest a different response to ER stress compared to the other cell lines and highlight the importance of understanding the diversity among cancer cells.

KEYWORDS:

Melanoma; Protein disulfide isomerase; Thapsigargin

PMID:
25912252
DOI:
10.1016/j.ijbiomac.2015.04.029
[Indexed for MEDLINE]

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