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Fig. 3 | Breast Cancer Research

Fig. 3

From: Cholesterol biosynthesis pathway as a novel mechanism of resistance to estrogen deprivation in estrogen receptor-positive breast cancer

Fig. 3

25-HC and 27-HC show SERM activity and can rescue the anti-proliferative effect of fulvestrant. wt-MCF7 and MCF7 LTED cells were treated with increasing (Log10M) concentrations of E2, 25-HC or 27-HC alone or in combination for 6 days. Proliferation was measured using TitreGlo to assess changes in cell viability and expressed as fold-change versus vehicle-treated control a, c or by assessment of changes in absolute cell number b, d. Data shown are representative of eight replicates per treatment for viability and three replicates per treatment for absolute cell number. Bars: ± SEM. e MCF7 LTED cells were treated with increasing concentrations of fulvestrant (ICI) alone or in combination with 25-HC or 27-HC (1000 nM). Cell viability was measured using TitreGlo and expressed as fold-change relative to vehicle-treated control. Data shown are representative of eight replicates per treatment. Bars: ± SEM. f Levels of 25-HC and 27-HC in whole cell extracts from wt-MCF7, MCF7 LTED, wt-HCC1428 and HCC1428 LTED were measured using LC-MS/MS. Data shown represent the median concentration (fmol/100,000 cells) from two experiments with three biological replicates per cell line. g In-silico analysis showing docking of both 27-HC and 25-HC to the LBD of ER based on the crystal structure. E2 estradiol, ER estrogen receptor alpha, HC hydroxycholesterol, LBD ligand-binding domain, LC-MS/MS liquid chromatography-tandem mass spectrometry, LTED, long-term estrogen deprivation, wt wild type

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