title: Estrogen Enhances the Expression of the Polyunsaturated Fatty Acid Elongase Elovl2 via ERα in Breast Cancer Cells.
abstract: Endocrine therapy is the first-line targeted adjuvant therapy for hormone-sensitive breast cancer. In view of the potential anticancer property of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) together with chemotherapy in estrogen receptor alpha (ERα) positive mammary tumors, we have explored the regulation by estradiol of the fatty acid desaturation and elongation enzymes involved in DHA synthesis in the human breast cancer cell line MCF7, which expresses ERα but not ERβ. We demonstrate a robust up-regulation in the expression of the fatty acid elongases Elovl2 and Elovl5 upon estradiol stimulation in MCF7 cells, which was sustained for more than 24 hours. Exposure with the ER inhibitor tamoxifen abolished specifically the Elovl2 but not the Elovl5 expression. Similarly, knock-down of ERα eliminated almost fully the Elovl2 but not the Elovl5 expression. Furthermore, ERα binds to one specific ERE within the Elovl2 enhancer in a ligand dependent manner. The involvement of ERα in the control of especially Elovl2, which plays a crucial role in DHA synthesis, may have potential implications in the treatment of breast cancer.
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors: Amanda
authors: A
authors: González-Bengtsson
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors: Abolfazl
authors: A
authors: Asadi
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors: Hui
authors: H
authors: Gao
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors: Karin
authors: K
authors: Dahlman-Wright
authors: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
authors: Anders
authors: http://orcid.org/0000-0001-5509-8824
authors: A
authors: Jacobsson
mesh_terms: D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D000081031:Fatty Acid Elongases; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D020218:Response Elements / Q000187:drug effects / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: C000630967:ELOVL2 protein, human; C000630954:ELOVL5 protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D005231:Fatty Acids, Unsaturated; D013629:Tamoxifen; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases