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Increased NOS2 predicts poor survival in estrogen receptor-negative breast cancer patients

  1. Author:
    Glynn, S. A.
    Boersma, B. J.
    Dorsey, T. H.
    Yi, M.
    Yfantis, H. G.
    Ridnour, L. A.
    Martin, D. N.
    Switzer, C. H.
    Hudson, R. S.
    Wink, D. A.
    Lee, D. H.
    Stephens, R. M.
    Ambs, S.

  2. Author Address

    [Glynn, Sharon A.; Boersma, Brenda J.; Dorsey, Tiffany H.; Martin, Damali N.; Hudson, Robert S.; Ambs, Stefan] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Glynn, Sharon A.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. [Yi, Ming; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21701 USA. [Yfantis, Harris G.; Lee, Dong H.] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA. [Ridnour, Lisa A.; Switzer, Christopher H.; Wink, David A.] NCI, Tumor Biol Sect, Radiat Biol Branch, CCR, Bethesda, MD 20892 USA.;Ambs, S, NCI, Human Carcinogenesis Lab, Ctr Canc Res, Room 3050B,37 Convent Dr MSC 4258, Bethesda, MD 20892 USA.;ambss@mail.nih.gov
    1. Year: 2010
    2. Date: Nov
  2. Journal: Journal of Clinical Investigation
    1. 120
    2. 11
    3. Pages: 3843-3854
  4. Type of Article: Article
  5. ISSN: 0021-9738
  1. Abstract:

    Inducible nitric oxide synthase (NOS2) is involved in wound healing, angiogenesis, and carcinogenesis. NOS2 upregulation and increased nitric oxide (NO) production affect the redox state of cells and can induce protein, lipid, and DNA modifications. To investigate whether NOS2 levels influence survival of breast cancer patients, we examined NOS2 expression and its association with tumor markers and survival in 248 breast tumors. In multivariable survival analysis, increased NOS2 predicted inferior survival in women with estrogen receptor alpha-negative (ER-negative) tumors. Microdissected tumor epithelium from ER-negative tumors with high NOS2 had increased IL-8 and a gene expression signature characteristic of basal-like breast cancer with poor prognosis. In cell culture, NO only induced selected signature genes in ER-negative breast cancer cells. ER transgene expression in ER-negative cells inhibited NO-induced upregulation of the stem cell marker CD44 and other proteins encoded by signature genes, but not of IL-8. Exposure to NO also enhanced cell motility and invasion of ER-negative cells. Last, pathway analysis linked the tumor NOS2 gene signature to c-Myc activation. Thus, NOS2 is associated with a basal-like transcription pattern and poor survival of ER-negative patients.

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External Sources

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  2. DOI: 10.1172/jci42059
  3. View record in Web of Science®
  4. WOS: 000283621800019

Library Notes

  1. Fiscal Year: FY2010-2011
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