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Updated: May 30, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Immunohistochemical analysis for cell regulatory proteins in bladder carcinogenesis induced by
Yuan Shi1, Lunbiao Cui, Guidong Dai
1Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China; Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.
Abstract:
To explore the cell cycle regulatory mechanism in bladder carcinogenesis promoted by terephthalic acid calculi (TPA-calculi), male Wistar rats were initiated with N-methyl-N-nitrosourea (MNU) (20mg/kg b.w. i.p.) twice a week for 4 weeks, and then given basal diet containing 5% TPA, 5% TPA plus 4% Sodium bicarbonate (NaHCO(3)) or 1% TPA for the next 22 weeks. Major regulatory proteins in G1 cell cycle checkpoint including p16(INK4a), cyclin-dependent kinase 4 (Cdk4), cyclin D(1), retinoblastoma protein (pRb) were determined during various stages of urinary bladder carcinogenesis by using immunohistochemistry. In MNU-5% TPA treated group, the incidences of overexpression of Cdk4, cyclin D(1) and pRb in papilloma were significantly higher than these in simple hyperplasia (p=0.023, p<0.001 and 0.001, respectively) and in PN hyperplasia (p=0.042, 0.012 and 0.002, respectively). The incidence of absent expression of p16(INK4a) in papilloma was much higher than that in simple hyperplasia (p=0.004) and in PN hyperplasia (p=0.02). Our results clearly reveal that the deregulation of p16(INK4a)-cyclin D(1)/Cdk4-pRb pathway is associated with bladder carcinogenesis promoted by TPA-calculi.
