title: RNAi-mediated knock-down of arylamine N-acetyltransferase-1 expression induces E-cadherin up-regulation and cell-cell contact growth inhibition.
abstract: 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.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Jacky M
authors.initials: JM
authors.lastname: Tiang
authors.forename: Neville J
authors.initials: NJ
authors.lastname: Butcher
authors.forename: Carleen
authors.initials: C
authors.lastname: Cullinane
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Humbert
authors.forename: Rodney F
authors.initials: RF
authors.lastname: Minchin
mesh_terms: D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000172:deficiency* / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D002450:Cell Communication / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics*; D007700:Kinetics; D051379:Mice; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D015820:Cadherins; D007527:Isoenzymes; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1