Transgenic mouse with human mutant p53 expression in the prostate epithelium
Corresponding Author
Ada Elgavish
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Department of Surgery, Division of Urology, University of Alabama at Birmingham, Birmingham, Alabama
Department of Genetics, Kaul Building, r. 624, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294.Search for more papers by this authorPhilip A. Wood
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorCarl A. Pinkert
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorIsam-Eldin Eltoum
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorTodd Cartee
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorJohn Wilbanks
Department of Surgery, Division of Urology, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorRoycelynn Mentor-Marcel
Department of Toxicology/Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorLiqun Tian
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorSamuel E. Scroggins
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorCorresponding Author
Ada Elgavish
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Department of Surgery, Division of Urology, University of Alabama at Birmingham, Birmingham, Alabama
Department of Genetics, Kaul Building, r. 624, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294.Search for more papers by this authorPhilip A. Wood
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorCarl A. Pinkert
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorIsam-Eldin Eltoum
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorTodd Cartee
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorJohn Wilbanks
Department of Surgery, Division of Urology, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorRoycelynn Mentor-Marcel
Department of Toxicology/Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorLiqun Tian
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorSamuel E. Scroggins
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
Search for more papers by this authorAbstract
Background
Apoptosis is disrupted in prostate tumor cells, conferring a survival advantage. p53 is a nuclear protein believed to regulate cancer progression, in part by inducing apoptosis. To test this possibility in future studies, the objective of the present study was to generate a transgenic mouse model expressing mutant p53 in the prostate (PR).
Methods
Transgene incorporation was tested using Southern analysis. Expression of mutant p53 protein was examined using immunofluorescence microscopy. Apoptosis in the PR was evaluated using the Tunnel method.
Results
A construct, consisting of the rat probasin promoter and a mutant human p53 fragment, was prepared and used to generate transgenic mice. rPB-mutant p53 transgene incorporation, as well as nuclear accumulation of mutant human p53 protein, was demonstrated. Prostatic intraepithelial neoplasia (PIN) III and IV were found in PR of 52-week old transgenic mice, whereas no pathological changes were found in the other organs examined. PR ability to undergo apoptosis following castration was reduced in rPB-mutant p53 mice as compared to non transgenic littermates.
Conclusions
Transgenic rPB-mutant p53 mice accumulate mutant p53 protein in PR, resulting in neoplastic lesions and reduced apoptotic potential in the PR. Breeding rPB-mutant p53 mice with mice expressing an oncogene in their PR will be useful in examining interactions of multiple genes that result in progression of slow growing prostate tumors expressing oncogenes alone to metastatic cancer. © 2004 Wiley-Liss, Inc.
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