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Cell transformation by the superoxide-generating oxidase Mox1

Author

Listed:
  • Young-Ah Suh

    (Emory University Medical School)

  • Rebecca S. Arnold

    (Emory University Medical School)

  • Bernard Lassegue

    (Emory University Medical School)

  • Jing Shi

    (Emory University Medical School)

  • Xiangxi Xu

    (Emory University Medical School)

  • Dan Sorescu

    (Emory University Medical School)

  • Andrew B. Chung

    (Emory University Medical School)

  • Kathy K. Griendling

    (Emory University Medical School)

  • J. David Lambeth

    (Emory University Medical School)

Abstract

Reactive oxygen species (ROS) generated in some non-phagocytic cells are implicated in mitogenic signalling and cancer1,2,3,4,5,6. Many cancer cells show increased production of ROS7, and normal cells exposed to hydrogen peroxide or superoxide show increased proliferation8 and express growth-related genes9,10,11. ROS are generated in response to growth factors, and may affect cell growth2,3,12,13, for example in vascular smooth-muscle cells6,13,14,15. Increased ROS in Ras-transformed fibroblasts correlates with increased mitogenic rate16. Here we describe the cloning of mox1, which encodes a homologue of the catalytic subunit of the superoxide-generating NADPH oxidase of phagocytes17,18, gp91phox. mox1 messenger RNA is expressed in colon, prostate, uterus and vascular smooth muscle, but not in peripheral blood leukocytes. In smooth-muscle cells, platelet-derived growth factor induces mox1 mRNA production, while antisense mox1 mRNA decreases superoxide generation and serum-stimulated growth. Overexpression of mox1 in NIH3T3 cells increases superoxide generation and cell growth. Cells expressing mox1 have a transformed appearance, show anchorage-independent growth and produce tumours in athymic mice. These data link ROS production by Mox1 to growth control in non-phagocytic cells.

Suggested Citation

  • Young-Ah Suh & Rebecca S. Arnold & Bernard Lassegue & Jing Shi & Xiangxi Xu & Dan Sorescu & Andrew B. Chung & Kathy K. Griendling & J. David Lambeth, 1999. "Cell transformation by the superoxide-generating oxidase Mox1," Nature, Nature, vol. 401(6748), pages 79-82, September.
    • Handle: RePEc:nat:nature:v:401:y:1999:i:6748:d:10.1038_43459
    DOI: 10.1038/43459
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    Cited by:

    1. Sigrid Noreng & Naruhisa Ota & Yonglian Sun & Hoangdung Ho & Matthew Johnson & Christopher P. Arthur & Kellen Schneider & Isabelle Lehoux & Christopher W. Davies & Kyle Mortara & Kit Wong & Dhaya Sesh, 2022. "Structure of the core human NADPH oxidase NOX2," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Elizabeth Zoneff & Yi Wang & Colin Jackson & Oliver Smith & Serena Duchi & Carmine Onofrillo & Brooke Farrugia & Simon E. Moulton & Richard Williams & Clare Parish & David R. Nisbet & Lilith M. Caball, 2024. "Controlled oxygen delivery to power tissue regeneration," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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