LXR Activation Down-regulates Lipid Raft Markers FLOT2 and DHHC5 in MCF-7 Breast Cancer Cells
LXR Activation Down-regulates Lipid Raft Markers FLOT2 and DHHC5 in MCF-7 Breast Cancer Cells
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DOI：
10.21873/anticanres.11792
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发表时间：
2017-08-01
影响因子：
2
通讯作者：
Nazih, Hassan
中科院分区：
文献类型：
--
作者：
Carbonnelle, Delphine;Luu, Trang H.;Nazih, Hassan
背景/目的：脂筏是质膜上富含胆固醇的微域。最近的研究强调，它们的完整性对于癌细胞的存活至关重要。肝脏 X 受体 (LXR) 在细胞胆固醇稳态中发挥核心作用，其刺激可抑制多种癌细胞系的增殖。本研究调查了 LXR 是否可以调节脂筏完整性，从而改变 MCF-7 乳腺癌细胞系的增殖。材料和方法：通过研究筏标记物 flotillin-2 (FLOT2) 和 DHHC5（棕榈酰化 FLOT2）的表达，以及研究磷酸-Akt 的表达，检查 LXR 激动剂 T0901317 对 MCF-7 脂筏完整性的影响。结果：我们证明 LXR 刺激会降低 MCF-7 细胞中 FLOT2 和 DHHC5 的 mRNA 和蛋白表达。 LXR 刺激还会降低 Akt 磷酸化及其在质膜上的定位。结论：我们首次证明 LXR 在乳腺癌模型中调节脂筏特定蛋白的转录。
Background/Aim: Lipid rafts are cholesterol-enriched microdomains of the plasma membrane. Recent studies have underlined that their integrity is critical for cancer cell survival. Liver X receptor (LXR) has a central role in cellular cholesterol homeostasis and its stimulation inhibits proliferation of several cancer cell lines. This study investigated whether LXR could modulate lipid rafts integrity and consequently alter proliferation of the MCF-7 breast cancer cell line. Materials and Methods: Effect of LXR agonist T0901317 on integrity of MCF-7 lipid rafts was examined by studying the expression of rafts marker flotillin-2 (FLOT2) and DHHC5, which palmitoylates FLOT2, and by studying the expression of phospho-Akt. Results: We demonstrated that LXR stimulation decreases mRNA and protein expression of FLOT2 and DHHC5 in MCF-7 cells. LXR stimulation also reduces Akt phosphorylation and its localization at the plasma membrane. Conclusion: We showed, for the first time, that LXR regulates transcription of specific proteins of lipid rafts in a breast cancer model.