Transformation of mammalian cells by overexpressing H2O2-generating peroxisomal fatty acyl-CoA oxidase

Su Chu, Qin Huang, Keith Alvares, Anjana V. Yeldandi, M. Sambasiva Rao, Janardan K. Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Peroxisome proliferators induce qualitatively predictable pleiotropic responses, including development of hepatocellular carcinomas in rats and mice despite the inability of these compounds to interact with and damage DNA directly. In view of the nongenotoxic nature of peroxisome proliferators, it has been postulated that hepatocarcinogenesis by this class of chemicals is due to a receptor-mediated process leading to transcriptional activation of H2O2-generating peroxisomal fatty acyl-CoA oxidase (ACOX) in liver. To test this hypothesis, we overexpressed rat ACOX in African green monkey kidney cells (CV-1 cells) under control of the cytomegalovirus promoter. A stably transfected CV-1 cell line overexpressing rat ACOX, designated CV-ACOX4, when exposed to a fatty acid substrate (150 μM linoleic acid) for 2-6 weeks, formed transformed foci, grew efficiently in soft agar, and developed adenocarcinomas when transplanted into nude mice. These findings indicate that sustained overexpression of H2O2-generating ACOX causes cell transformation and provide further support for the role of peroxisome proliferation in hepatocarcinogenesis induced by peroxisome proliferators.

Original languageEnglish (US)
Pages (from-to)7080-7084
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number15
StatePublished - Jul 18 1995


  • fatty acid β- oxidation
  • peroxisome proliferation
  • peroxisome proliferators

ASJC Scopus subject areas

  • General


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