Protein disulfide isomerases: Impact of thapsigargin treatment on their expression in melanoma cell lines.
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.
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.
Zélia
Z
Silva
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.
Teresa
T
Veríssimo
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.
Paula A
PA
Videira
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.
Carlos
C
Novo
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001414:Bacitracin / Q000494:pharmacology; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D011490:Protein Disulfide Reductase (Glutathione) / Q000235:genetics / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D001414:Bacitracin; D019284:Thapsigargin; D011490:Protein Disulfide Reductase (Glutathione); C546436:TMX4 protein, human; C526506:PDIA5 protein, human; C496931:PDIA6 protein, human; D019704:Protein Disulfide-Isomerases; C498879:TMX3 protein, human
Melanoma; Protein disulfide isomerase; Thapsigargin