Division of Life Sciences, College of Life Sciences and Biotechnology, Research Institute for Natural Sciences, Korea University, Seoul, 136-701, South Korea, and.
J Proteome Res. 2013 Feb 1;12(2):605-14. doi: 10.1021/pr300651m. Epub 2013 Jan 4.
Since detergent-resistant lipid rafts play important roles in multidrug resistance (MDR), their comprehensive proteomics could provide new insights to understand the underlying molecular mechanism of MDR in cancer cells. In the present work, lipid rafts were isolated from MCF-7 and adriamycin-resistant MCF-7/ADR cells and their proteomes were analyzed by label-free quantitative proteomics. Polymerase I and transcript release factor (PTRF)/cavin-1 was measured to be upregulated along with multidrug-resistant P-glycoprotein, caveolin-1, and serum deprivation protein response/cavin-2 in the lipid rafts of MCF-7/ADR cells. PTRF knockdown led to reduction in the amount of lipid rafts on the surface of MCF7/ADR cells as determined by cellular staining with lipid raft-specific dyes such as S-laurdan2 and FITC-conjugated cholera toxin B. PTRF knockdown also reduced MDR in MCF-7/ADR cells. These data indicate that PTRF is necessary for MDR in cancer cells via the fortification of lipid rafts.
由于去污剂抗性脂质筏在多药耐药性 (MDR) 中发挥着重要作用，因此对其进行全面的蛋白质组学研究可以为理解癌细胞中 MDR 的潜在分子机制提供新的见解。在本研究中，从 MCF-7 和阿霉素耐药 MCF-7/ADR 细胞中分离出脂质筏，并通过无标记定量蛋白质组学对其蛋白质组进行分析。结果表明，随着多药耐药性 P-糖蛋白、质膜窖蛋白-1（caveolin-1）和血清剥夺蛋白反应/窖蛋白-2在 MCF-7/ADR 细胞的脂质筏中上调，聚合酶 I 和转录释放因子 (PTRF)/窖蛋白-1 (cavin-1) 的含量也随之增加。通过用脂质筏特异性染料（如 S-软脂酰-2-二氢荧光素和 FITC 缀合霍乱毒素 B）对 MCF7/ADR 细胞进行细胞染色，发现 PTRF 敲低导致 MCF-7/ADR 细胞表面脂质筏的数量减少。PTRF 敲低也降低了 MCF-7/ADR 细胞的多药耐药性。这些数据表明，PTRF 通过强化脂质筏在癌细胞的多药耐药性中是必需的。
