title: 17β-estradiol induces stearoyl-CoA desaturase-1 expression in estrogen receptor-positive breast cancer cells.
abstract: BACKGROUND
  To sustain cell growth, cancer cells exhibit an altered metabolism characterized by increased lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1) catalyzes the production of monounsaturated fatty acids that are essential for membrane biogenesis, and is required for cell proliferation in many cancer cell types. Although estrogen is required for the proliferation of many estrogen-sensitive breast carcinoma cells, it is also a repressor of SCD-1 expression in liver and adipose. The current study addresses this apparent paradox by investigating the impact of estrogen on SCD-1 expression in estrogen receptor-α-positive breast carcinoma cell lines.
  
  
  METHODS
  MCF-7 and T47D mammary carcinomas cells and immortalized MCF-10A mammary epithelial cells were hormone-starved then treated or not with 17β-estradiol. SCD-1 activity was assessed by measuring cellular monounsaturated/saturated fatty acid (MUFA/SFA) ratios, and SCD-1 expression was measured by qPCR, immunoblot, and immunofluorescence analyses. The role of SCD-1 in cell proliferation was measured following treatment with the SCD-1 inhibitor A959372 and following SCD-1 silencing using siRNA. The involvement of IGF-1R on SCD-1 expression was measured using the IGF-1R antagonist AG1024. The expression of SREBP-1c, a transcription factor that regulates SCD-1, was measured by qPCR, and by immunoblot analyses.
  
  
  RESULTS
  17β-estradiol significantly induced cell proliferation and SCD-1 activity in MCF-7 and T47D cells but not MCF-10A cells. Accordingly, 17β-estradiol significantly increased SCD-1 mRNA and protein expression in MCF-7 and T47D cells compared to untreated cells. Treatment of MCF-7 cells with 4-OH tamoxifen or siRNA silencing of estrogen receptor-α largely prevented 17β-estradiol-induced SCD-1 expression. 17β-estradiol increased SREBP-1c expression and induced the mature active 60 kDa form of SREBP-1. The selective SCD-1 inhibitor or siRNA silencing of SCD-1 blocked the 17β-estradiol-induced cell proliferation and increase in cellular MUFA/SFA ratios. IGF-1 also induced SCD-1 expression, but to a lesser extent than 17β-estradiol. The IGF-1R antagonist partially blocked 17β-estradiol-induced cell proliferation and SCD-1 expression, suggesting the impact of 17β-estradiol on SCD-1 expression is partially mediated though IGF-1R signaling.
  
  
  CONCLUSIONS
  This study illustrates for the first time that, in contrast to hepatic and adipose tissue, estrogen induces SCD-1 expression and activity in breast carcinoma cells. These results support SCD-1 as a therapeutic target in estrogen-sensitive breast cancer.
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine Maillet Ave, Moncton, NB, E1A 3E9, Canada. eab3548@umoncton.ca.|Atlantic Cancer Research Institute, Moncton, NB, Canada. eab3548@umoncton.ca.
authors.forename: Anissa
authors.initials: A
authors.lastname: Belkaid
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine Maillet Ave, Moncton, NB, E1A 3E9, Canada. esd0831@umoncton.ca.
authors.forename: Sabrina R
authors.initials: SR
authors.lastname: Duguay
authors.affiliation: Atlantic Cancer Research Institute, Moncton, NB, Canada. rodneyo@canceratl.ca.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Ouellette
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, 18 Antonine Maillet Ave, Moncton, NB, E1A 3E9, Canada. marc.surette@umoncton.ca.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Surette
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004958:Estradiol; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase