Abstract:
Arylamine N-acetyltransferase 1 (NAT1) is frequently upregulated in breast cancer. An unbiased analysis of proteomes of parental MDA-MB-231 breast cancer cells and two separate NAT1 knockout (KO) cell lines were performed. Among 4,890 proteins identified, 737 and 651 proteins were found significantly (p < 0.01) upregulated and downregulated, respectively, in NAT1 KO cells, compared to the parental cells. Each set of proteins was analyzed to identify Gene Ontology biological processes, molecular functions, and cellular components that were enriched in the set. Among the proteins upregulated in NAT1 KO cells, processes associated with MHC major histocompatibility complex I-mediated antigen presentation were significantly enriched. Multiple processes involved in mitochondrial functions were collectively downregulated in NAT1 KO cells, including multiple subunits of mitochondrial ATP synthase (Complex V of the electron transport chain). This was accompanied by a reduction in cell cycle-associated proteins and an increase in pro-apoptotic pathways in NAT1 KO cells. The current dataset contains additional representations of the biological processes and components that are differentially enriched in NAT1 KO MDA-MB-231 cells and will serve as a basis for generating novel hypotheses regarding the role of NAT1 in breast cancer. Data are available via ProteomeXchange with identifier PXD035953.
摘要:
芳胺N-乙酰转移酶1(NAT1)在乳腺癌中经常上调。对亲本MDA-MB-231乳腺癌细胞和两个单独的NAT1敲除(KO)细胞系的蛋白质组进行无偏分析。在鉴定的4,890种蛋白质中,发现737和651蛋白显著上调和下调(p<0.01),分别,在NAT1KO细胞中,与亲代细胞相比。分析每组蛋白质以鉴定基因本体论生物学过程,分子功能,和细胞成分在集合中富集。在NAT1KO细胞中上调的蛋白质中,与MHC主要组织相容性复合物I介导的抗原呈递相关的过程显著富集.参与线粒体功能的多个过程在NAT1KO细胞中共同下调,包括线粒体ATP合酶的多个亚基(电子传递链的复合物V)。这伴随着NAT1KO细胞中细胞周期相关蛋白的减少和促凋亡途径的增加。当前的数据集包含在NAT1KOMDA-MB-231细胞中差异富集的生物过程和成分的其他表示,并将作为产生有关NAT1在乳腺癌中的作用的新假设的基础。数据可通过具有标识符PXD035953的ProteomeXchange获得。