This work is licensed under a Figure 3.
27HC activates LXRE- and ERE-dependent transcription in endometrial epithelial cancer cells and alters proliferation. The cholesterol metabolite 27-hydoxycholesterol (27HC) is the endogenous agonist for LXR and is also classified as selective oestrogen receptor modulator. The impact of 27HC on LXRE- (A, B and C) and ERE-dependent (D, E and F) transcription was investigated by luciferase reporter assay in endometrial cancer cell lines; Ishikawa, RL95 and MFE280. 27HC significantly increased LXRE-dependent transcription in a dose-dependent manner in each endometrial cancer cell line. 27HC stimulated ERE-dependent transcription only at lower concentrations and was significantly increased by 10−8 M 27HC (P < 0.01) and maximally stimulated by 10−7 M 27HC (P < 0.0001). The 27HC effect was abrogated by co-incubation with the antiestrgoen Fulvestrant (ICI 182,780; ICI) at all concentrations of 27HC (D). 27HC did not increase ERE-dependent transcription in RL95 (E) and was only increased by 10−5 M 27HC (P < 0.05) in MFE280 cells (F). Cell proliferation was assessed by CyQuant direct proliferation assay in each cell line (G, H and I). Proliferation of Ishikawa cells was increased by 10−8 M (P < 0.01), 10−7 M (P < 0.01) and 10−6 M (P < 0.01) 27HC but decreased by 10−5 M 27HC (P < 0.0001; G). Proliferation of RL95 cells was increased by 10−7 M (P < 0.001), 10−6 M (P < 0.01) and 10−5 M (P < 0.001) 27HC (H). 27HC did not affect proliferation in MFE280 cells (I). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. One sample t test and a theoretical mean of 1. All data are presented as mean ± s.e.m.