Expression Of Liver X Receptors In Human Breast Cancer And Its Effect On Proliferation Of Breast Cancer Cell Line MCF-7

Objective: Liver X receptors(LXR) including LXRαand LXRβ are nuclearreceptors activated by ligand, which are closely related to metabolize of cholesterol,fatty acid, glucose and inflammation.This study was to investigate the expression ofLXRs in human breast cancer, and its effect and mechanism on proliferation of breastcancer cell line MCF-7.Methods:①The expression of LXRα and LXRβ in human breast cancer(107cases)were examined by immunohistochemical technique, and the positive rates and thechange of average gray value were analyzed by micro-image analysis system.②Human breast cancer MCF-7cells maintained in DMEM at37℃were treated withthe LXR agonists T0901317(10μM), the proliferation assay was performed by MTTand FCM after72hours.③MCF-7cells were exposed to T0901317with differentlevels（0、5、10、20μM) for24hours or exposed to10μM T0901317for increasingperiods of time（0、6、12、24h）. Real-time quantitative PCR(RT-PCR) and westernblotting were used to determine mRNA and protein levels for cyclin D1(CD1) andcyclin E(CE).Immunoprecipitation(IP)-western blot analysis was used to determinethe levels of compound for p300/LXRα or p300/c-fos. Our experiment also observedthe proliferation rate and cyclin D1expression of MCF-7cells knockdown theexpression of LXRα by siRNA.Results: Our experiments show that the proteins of LXRα and LXRβ were notobviously expressed in normal breast tissues, but positive expression ratio andintensity of LXRα has significantly increased in breast cancer tissues including ductalcarcinoma in situ(DCIS) and invasive ductal carcinoma(IDC), while LXRβ has no expressed in breast cancer tissues. The MCF-7cells treated with LXR agonistT0901317showed decreased proliferation compared with the comtrol MCF-7cells.T0901317can obviously decrease the expression of cyclin D1mRNA and proteinlevels in dose-and time-dependent manner, but has no effect on cyclin E expression.T0901317recruited p300to LXRα in MCF-7cells and reduced binding of p300toc-Fos. Pretreatment with siRNA for LXRα can significantly reverse the inhibitedeffect of T0901317on cyclin D1expression in MCF-7cells.Conclusions: These findings suggest that the expression of LXRα is increased inbreast cancer, and activation of LXRα by T0901317inhibits the proliferation of theMCF-7cells, which may have relationship with the reduced binding of p300to c-Fosand resulting in the decreased expression of cyclin D1.