RNAi-mediated knock-down of arylamine N-acetyltransferase-1 expression induces E-cadherin up-regulation and cell-cell contact growth inhibition

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arylamine N-Acetyltransferase / deficiency*
  • Arylamine N-Acetyltransferase / genetics*
  • Cadherins / genetics*
  • Cell Communication / genetics*
  • Cell Proliferation
  • Cell Survival / genetics
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Female
  • Gene Knockdown Techniques*
  • HT29 Cells
  • Humans
  • Isoenzymes / deficiency*
  • Isoenzymes / genetics*
  • Kinetics
  • Mice
  • RNA Interference*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Up-Regulation / genetics*


  • Cadherins
  • Isoenzymes
  • RNA, Messenger
  • RNA, Small Interfering
  • Arylamine N-Acetyltransferase
  • N-acetyltransferase 1