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Histologic analysis of bladder cancer: A new mouse model
Author(s) -
Nagar Michael Shaun,
Puzio Anna,
AbateShen Cory,
May Michael
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a382
Subject(s) - pten , bladder cancer , cancer , cancer research , pathology , loss function , biology , carcinoma , urothelium , phenotype , carcinogenesis , urinary bladder , medicine , apoptosis , gene , biochemistry , pi3k/akt/mtor pathway
Background: The progression of Papillary Urothelial Neoplasm of Low Malignant Potential and Urothelial Carcinoma In Situ into bladder cancer is currently not well understood. Design: We developed an autochthonous mouse model that utilizes adenovirus‐Cre to inactivate tumor suppressor functions, Pten and p53. We then characterized the histologic pattern of the resultant tumors and compared them to human bladder carcinomas. Histologic data from mutant mice that had been infected with adeno‐Cre 3–6 months prior to sacrifice was obtained. The R26R control mouse bladder was compared to R26r p53 loss of function mice, R26r Pten loss of function mice, and to the combination of R26r p53 and Pten loss of function mice. Urothelial thickness, dysplastic changes, and histologic characterization of neoplasms were noted. Results: High grade invasive urothelial carcinoma was found exclusively in mice containing a combination of loss of function Pten and p53 with high penetrance. Conclusion: The invasive urothelial cancer observed was strikingly similar to the appearance of human invasive bladder cancer. More importantly, the model created in this study gives way to a greater understanding of the molecular physiology of bladder cancer formation in both mice and men.