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Docosahexaenoic Acid Activates Some SREBP‐2 Targets Independent of Cholesterol and ER Stress in SW620 Colon Cancer Cells
Author(s) -
Størvold Gro Leite,
Fleten Karianne Giller,
Olsen Cathrine Goberg,
Follestad Turid,
Krokan Hans Einar,
Schønberg Svanhild Arentz
Publication year - 2009
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-009-3324-4
Subject(s) - sterol regulatory element binding protein , docosahexaenoic acid , npc1 , cholesterol , cancer research , chemistry , biology , microbiology and biotechnology , biochemistry , endocrinology , medicine , sterol , fatty acid , polyunsaturated fatty acid , cell , endosome
The SREBP‐2 transcription factor is mainly activated by low cellular cholesterol levels. However, other factors may also cause SREBP‐2 activation. We have previously demonstrated activation of SREBP‐2 by the polyunsaturated fatty acid docosahexaenoic acid (DHA) in SW620 colon cancer cells. Despite activation of SREBP‐2, only a few target genes were induced and cholesterol biosynthesis was reduced. In the present study, gene expression analysis at early time points verified the previously observed SREBP‐2 target gene expression pattern. Activation of SREBP‐2 using siRNAs targeting Niemann Pick C1 protein (NPC1) led to increased expression of all SREBP target genes examined, indicating that activation of some SREBP‐2 target genes is inhibited during DHA‐treatment. Cholesterol supplementation during DHA treatment did not abolish SREBP‐2 activation. We also demonstrate that activation of SREBP‐2 is independent of ER stress and eIF2α phosphorylation, which we have previously observed in DHA‐treated cells. Thapsigargin‐induced ER stress repressed expression of SREBP‐2 target genes, but with a different pattern than observed in DHA‐treated cells. Moreover, oleic acid (OA) treatment, which does not induce ER stress in SW620 cells, led to activation of SREBP‐2 and induced a target gene expression pattern similar to that of DHA‐treated cells. These results indicate that DHA and OA may activate SREBP‐2 and inhibit activation of SREBP‐2 target genes through a mechanism independent of cholesterol level and ER stress.