Krajewski Adrian, Gagat Maciej, Żuryń Agnieszka, Hałas-Wiśniewska Marta, Grzanka Dariusz, Grzanka Alina
Department of Histology and Embryology, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, 85‑092 Bydgoszcz, Poland.
Department of Clinical Pathomorphology, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, 85‑092 Bydgoszcz, Poland.
Oncol Rep. 2020 Mar;43(3):765-772. doi: 10.3892/or.2020.7465. Epub 2020 Jan 14.
Cyclin F is a non‑canonical cyclin which is a part of the SKP1‑CUL1‑F‑box protein (SCF) E3 ubiquitin‑protein ligase complex. Cyclin F is responsible for target recognition, ubiquitination, and degradation of various molecular targets. This protein also controls genome stability through the degradation of ribonucleotide reductase subunit M2 (RRM2). In the present study, the difference between cyclin F expression in cell lines derived from primary and metastatic melanoma, A375 and RPMI‑7951, respectively, were investigated using a western blot analysis and flow cytometry assays. A decrease in cyclin F expression in the A375 cells and an increase in RPMI‑7951 cells after cisplatin treatment were observed. These changes may be related to a mutation in p53 in the RPMI‑7951 cell line. Flow cytometry was conducted to observe that the RPMI‑7951 cell line exhibited greater susceptibility to cisplatin, associated with lack of proper cell cycle control. Therefore, it is possible that cyclin F may modulate drug response in melanoma. The presented data describe cyclin F as a new potential factor that contributes to drug resistance in melanoma patients.
细胞周期蛋白F是一种非典型细胞周期蛋白,是SKP1-CUL1-F盒蛋白(SCF)E3泛素蛋白连接酶复合物的一部分。细胞周期蛋白F负责各种分子靶标的识别、泛素化和降解。该蛋白还通过降解核糖核苷酸还原酶亚基M2(RRM2)来控制基因组稳定性。在本研究中,分别使用蛋白质免疫印迹分析和流式细胞术检测,研究了源自原发性和转移性黑色素瘤的细胞系A375和RPMI-7951中细胞周期蛋白F表达的差异。观察到顺铂处理后A375细胞中细胞周期蛋白F表达降低,而RPMI-7951细胞中细胞周期蛋白F表达增加。这些变化可能与RPMI-7951细胞系中p53的突变有关。进行流式细胞术观察到,RPMI-7951细胞系对顺铂表现出更高的敏感性,这与缺乏适当的细胞周期控制有关。因此,细胞周期蛋白F有可能调节黑色素瘤中的药物反应。所呈现的数据将细胞周期蛋白F描述为导致黑色素瘤患者耐药性的一个新的潜在因素。