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Titolo:
DEVELOPMENT, PROGRESSION, AND ANDROGEN-DEPENDENCE OF PROSTATE TUMORS IN PROBASIN LARGE T-ANTIGEN TRANSGENIC MICE - A MODEL FOR PROSTATE-CANCER
Autore:
KASPER S; SHEPPARD PC; YAN YL; PETTIGREW N; BOROWSKY AD; PRINS GS; DODD JG; DUCKWORTH ML; MATUSIK RJ;
Indirizzi:
VANDERBILT UNIV,MED CTR,DEPT UROL SURG,A-1302 MED CTR N NASHVILLE TN 37232 VANDERBILT UNIV,MED CTR,DEPT PATHOL NASHVILLE TN 37232 UNIV ILLINOIS,DEPT UROL CHICAGO IL 00000 UNIV MANITOBA,DEPT PHYSIOL WINNIPEG MB CANADA UNIV MANITOBA,DEPT PATHOL WINNIPEG MB R3T 2N2 CANADA
Titolo Testata:
Laboratory investigation
fascicolo: 3, volume: 78, anno: 1998,
pagine: 319 - 333
SICI:
0023-6837(1998)78:3<319:DPAAOP>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
ATYPICAL ADENOMATOUS HYPERPLASIA; INTRAEPITHELIAL NEOPLASIA; RECEPTOR GENE; RETINOBLASTOMA GENE; SUPPRESSOR GENES; CARCINOMA; P53; EXPRESSION; CELLS; MOUSE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
71
Recensione:
Indirizzi per estratti:
Citazione:
S. Kasper et al., "DEVELOPMENT, PROGRESSION, AND ANDROGEN-DEPENDENCE OF PROSTATE TUMORS IN PROBASIN LARGE T-ANTIGEN TRANSGENIC MICE - A MODEL FOR PROSTATE-CANCER", Laboratory investigation, 78(3), 1998, pp. 319-333

Abstract

Probasin (PB) gene product is prostate-specific, epithelial cell in origin, and androgen-regulated. A large 12-kb promoter fragment of the PB gene (LPB) was linked to the simian virus 40 (SV40) large T antigen(Tag) deletion mutant (that removes the expression of the small t antigen) to deliver consistently high levels of transgene expression to the transgenic mouse prostate. Seven male founders, their male offspring, and all the male offspring from two female founders developed at least prostatic epithelial cell hyperplasia by 10 weeks of age, indicating that the incidence of transformation was 100%. Tumorigenesis in theLPB-Tag animals progressed in a manner similar to that observed in the human prostate. Initially, multifocal proliferating lesions were detected in the prostatic epithelium, which continued to progress into hyperplasia involving the entire epithelium and then low-grade dysplasia. Reactive stromal proliferation was induced and continued to develop throughout the progression to high-grade dysplasia, carcinoma in situ,and adenocarcinoma. Immunohistochemical studies indicated that most stromal cells stained positively for both androgen receptor and smooth muscle alpha-actin, suggesting that stromal overgrowth largely represented mesenchymal cells that had differentiated into smooth muscle cells. Epithelial cell transformation was accompanied by the down-regulation of differentiated function, as suggested by the loss of dorsolateral prostate-specific secretory proteins. Tumor growth was regarded as androgen-dependent because tumors regressed in animals castrated at 11 weeks of age, and androgen treatment restored both epithelial/stromal cell ratio and tumor growth. Furthermore, small populations of prostatic epithelial cells in castrated animals continued to proliferate, suggesting the potential for androgen-independent growth. Although prostatic metastasis to other organs was not observed, local invasion was detected. In summary, the LPB-Tag animal model is unique in that it is the only model generated with the Tag alone, thereby eliminating any influences of the small t antigen on prostate tumor formation. Moreover,this model undergoes molecular changes similar to those found in human prostate including: (a) the multi-focal nature of tumorigenesis, (b)the progressive histopathologic changes from low-to high-grade dysplasia similar to human prostatic intraepithelial neoplasia, (c) stimulation of reactive stromal proliferation, and (d) the androgen-dependent growth of the primary tumor. Thus, the LPB-Tag prostate tumor model will be useful for studying the sequential mechanisms underlying the development of multistep tumorigenesis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 17:41:56