School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland, Australia.
PLoS One. 2011 Feb 9;6(2):e17031. doi: 10.1371/journal.pone.0017031.
Arylamine N-acetyltransferase-1 (NAT1) is an enzyme that catalyzes the biotransformation of arylamine and hydrazine substrates. It also has a role in the catabolism of the folate metabolite p-aminobenzoyl glutamate. Recent bioinformatics studies have correlated NAT1 expression with various cancer subtypes. However, a direct role for NAT1 in cell biology has not been established. In this study, we have knocked down NAT1 in the colon adenocarcinoma cell-line HT-29 and found a marked change in cell morphology that was accompanied by an increase in cell-cell contact growth inhibition and a loss of cell viability at confluence. NAT1 knock-down also led to attenuation in anchorage independent growth in soft agar. Loss of NAT1 led to the up-regulation of E-cadherin mRNA and protein levels. This change in E-cadherin was not attributed to RNAi off-target effects and was also observed in the prostate cancer cell-line 22Rv1. In vivo, NAT1 knock-down cells grew with a longer doubling time compared to cells stably transfected with a scrambled RNAi or to parental HT-29 cells. This study has shown that NAT1 affects cell growth and morphology. In addition, it suggests that NAT1 may be a novel drug target for cancer therapeutics.
芳香胺 N-乙酰基转移酶 1（NAT1）是一种酶，可催化芳香胺和肼类底物的生物转化。它在叶酸代谢物 p-氨基苯甲酰谷氨酸的分解代谢中也具有作用。最近的生物信息学研究将 NAT1 表达与各种癌症亚型相关联。然而，NAT1 在细胞生物学中的直接作用尚未确定。在这项研究中，我们在结肠腺癌细胞系 HT-29 中敲低了 NAT1，发现细胞形态发生了明显变化，细胞间接触生长抑制增加，细胞活力在汇合时丧失。NAT1 敲低也导致软琼脂中锚定独立生长的减弱。NAT1 的缺失导致 E-钙粘蛋白 mRNA 和蛋白水平的上调。E-钙粘蛋白的这种变化不是由于 RNAi 脱靶效应引起的，在前列腺癌细胞系 22Rv1 中也观察到了这种变化。在体内，与稳定转染 scrambled RNAi 的细胞或亲本 HT-29 细胞相比，NAT1 敲低细胞的生长倍增时间更长。这项研究表明，NAT1 影响细胞的生长和形态。此外，它表明 NAT1 可能是癌症治疗的新的药物靶点。
