High concentration calcitriol induces endoplasmic reticulum stress related gene profile in breast cancer cells.
Calcitriol, the active form of vitamin D, is known for its anticancer properties including induction of apoptosis as well as the inhibition of angiogenesis and metastasis. Understanding the mechanisms of action for calcitriol will help with the development of novel treatment strategies. Since vitamin D exerts its cellular actions via binding to its receptor and by altering expressions of a set of genes, we aimed to evaluate the effect of calcitriol on transcriptomic profile of breast cancer cells. We previously demonstrated that calcitriol alters endoplasmic reticulum (ER) stress markers, therefore in this study we have focused on ER-stress-related genes to reveal calcitriols action on these genes in particular. We have treated breast cancer cell lines MCF-7 and MDA-MB-231 with previously determined IC50concentrations of calcitriol and evaluated the transcriptomic alterations via microarray. During analysis, only genes altered by at least 2-fold with a P value < 0.05 were taken into consideration. Our findings revealed an ER-stress-associated transcriptomic profile induced by calcitriol. Induced genes include genes with a pro-survival function (NUPR1, DNAJB9, HMOX1, LCN2, and LAMP3) and with a pro-death function (CHOP (DDIT3), DDIT4, NDGR1, NOXA, and CLGN). These results suggest that calcitriol induces an ER-stress-like response inducing both pro-survival and pro-death transcripts in the process.
Ege University, School of Medicine, Department of Medical Biochemistry, Bornova, Izmir 35100, Turkey.|Ege University, School of Medicine, Department of Medical Biochemistry, Bornova, Izmir 35100, Turkey.
Ali Burak
AB
Ozkaya
Ege University, School of Medicine, Department of Medical Biochemistry, Bornova, Izmir 35100, Turkey.|Ege University, School of Medicine, Department of Medical Biochemistry, Bornova, Izmir 35100, Turkey.
Handan
H
Ak
Ege University, School of Medicine, Department of Medical Biochemistry, Bornova, Izmir 35100, Turkey.|Ege University, School of Medicine, Department of Medical Biochemistry, Bornova, Izmir 35100, Turkey.
Hikmet Hakan
HH
Aydin
D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D058977:Molecular Sequence Annotation; D009928:Organ Specificity; D015398:Signal Transduction; D059467:Transcriptome
D051017:Apoptosis Regulatory Proteins; D002117:Calcitriol
ER stress; calcitriol; cancer; réponse aux protéines non repliées; stress du RE; unfolded protein response; vitamin D; vitamine D