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Urothelial Overexpression of Insulin-Like Growth Factor-1 Increases Susceptibility to p-Cresidine-Induced Bladder Carcinogenesis in Transgenic Mice

  1. Author:
    Hursting, S. D.
    Perkins, S. N.
    Lavigne, J. A.
    Beltran, L.
    Haines, D. C.
    Hill, H. L.
    Alvord, W. G.
    Barrett, J. C.
    DiGiovanni, J.

  2. Author Address

    Hursting, Stephen D.; Perkins, Susan N.] Univ Texas Austin, Dept Nutr Sci, Austin, TX 78712 USA. [Hursting, Stephen D.; Beltran, Linda, DiGiovanni, John] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA. [Lavigne, Jackie A.] NCI, Off Educ, Rockville, MD USA. [Haines, Diana C.; Hill, Heather L.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Alvord, W. Gregory] Data Management Serv Inc, Frederick, MD USA. [Barrett, J. Carl] Novartis Inst BioMed Res Inc, Cambridge, MA USA.
    1. Year: 2009
  2. Journal: Molecular Carcinogenesis
    1. 48
    2. 8
    3. Pages: 671-677
  4. Type of Article: Article
  1. Abstract:

    To establish a role for insulin-like growth factor-1 (IGF-1) in bladder cancer susceptibility, we tested the effect of p-cresidine, a potent bladder carcinogen, in transgenic (TG) mice with human IGF-1 expression in the bladder driven by the bovine keratin 5 promoter (referred to as BK5.IGF-1 TG mice). Indomethacin was also tested to determine if the cyclooxygenase (COX) pathway is a target for bladder cancer prevention in this model. Thirty-three female BK5.IGF-1 TG mice and 29 female nontransgenic littermates were randomized to the following treatments: (1) AIN-76A diet, (2) AIN-76A diet with 0.5% p-cresidine, or (3) AIN-76A diet with 0.5% p-cresidine+0.00075% indomethacin. BK5.IGF-1 TG mice, with twofold greater total serum IGF-1 than nontransgenic mice, exhibited greatly increased susceptibility to p-cresidine-induced bladder tumors compared to nontransgenic mice. The most common type of bladder tumor in the BK5.IGF-1 TG mice was transitional cell carcinoma, which is the predominant type of bladder cancer observed in developed countries. indomethacin inhibition of bladder tumor development in BK5.IGF-1 TG mice was not statistically significant. These results present further evidence for the role of IGF-1 in bladder cancer progression. In addition, these transgenic mice provide a useful model for studying the role of the IGF-1 pathway in bladder carcinogenesis and its prevention. (C) 2009 Wiley-Liss, Inc.

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  2. DOI: 10.1002/mc.20548
  3. PMID: 19415693

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