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Differential expression of nitric oxide synthase II and prostaglandin endoperoxide H synthase-2 in conditionally immortal mouse colon epithelial cells contrasting in Apc genotype

  1. Author:
    Mei, J. M.
    Hord, N. G.
    Phang, J. M.
    1. Year of Conference: 1997
  2. Conference Name: Annual Meeting of the American Association for Cancer Research
    1. 38
    2. Pages: A3872
  4. Type of Work: Meeting Abstract
  1. Abstract:

    Elevated expression of nitric oxide synthase II (NOS II) is associated with chronic infection and inflammation. Subsequent overproduction of NO may contribute to DNA damage and carcinogenesis. Similarly, prostaglandin endoperoxide H synthase-2 (PGHS-2) overexpression has been associated with colorectal tumorigenesis. Germline and somatic mutations in the Adenomatous polyposis coli (Apc) gene are seminal events in colorectal tumorigenesis. Recent data suggesting that wild type APC influences colon epithelial apoptosis led us to hypothesize that epithelial cells contrasting in Apc genotype would respond differentially to inflammatory stimuli. Using conditionally immortal mouse colon epithelial cells of distinct Apc genotypes (YAMC, Apc +/+; IMCE, Apc +/-), we demonstrated by Western immunoblotting that expression of NOS II and PGHS-2 induced by lipopolysaccharide and interferon-gamma in IMCE cells was significantly higher compared to that of YAMC cells. This induction was accompanied by production of NO, as assessed by the Griess reaction, and was inhibited by NG-L-nitro-arginine-methyl-ester. Studies are underway to identify Apc genotype-specific apoptotic regulators.

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