Prostate cancer progression, metastasis, and gene expression in transgenic mice

We previously reported that a transgenic mouse line containing the fetal globin promoter linked to the SV40 T antigen (T Ag) viral oncogene (Ggamma/T-15) resulted in prostate tumors. In this study, we further explored tumor origin, frequency, invasiveness, androgen sensitivity, and gene expression p...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1997-03, Vol.57 (5), p.900-906
Main Authors: PEREZ-STABLE, C, ALTMAN, N. H, MEHTA, P. P, DEFTOS, L. J, ROOS, B. A
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Androgens - physiology
Animals
Antigens, Polyomavirus Transforming - genetics
Biological and medical sciences
Chromogranin A
Chromogranins - metabolism
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Genes, bcl-2
Genes, myc
Genes, p53
Genes, Retinoblastoma
Keratins - metabolism
Male
Medical sciences
Mice
Mice, Transgenic
Neoplasm Metastasis
Nephrology. Urinary tract diseases
Orchiectomy
Precancerous Conditions - pathology
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
RNA, Messenger - genetics
Time Factors
Tumors of the urinary system
Urinary tract. Prostate gland
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Summary:We previously reported that a transgenic mouse line containing the fetal globin promoter linked to the SV40 T antigen (T Ag) viral oncogene (Ggamma/T-15) resulted in prostate tumors. In this study, we further explored tumor origin, frequency, invasiveness, androgen sensitivity, and gene expression pattern. T Ag was detected in adult but not fetal and neonatal prostates, suggesting a role for androgens in tumor progression. However, castration shortly after prostate morphogenesis did not prevent tumor development, suggesting an androgen-independent phenotype. Tumors originated within ventral or dorsal prostate lobes and involved intraepithelial neoplasia, rapid growth in the pelvic region, and metastasis to lymph nodes and distant sites. In addition, the primary cancers could be propagated in nude mice or nontransgenic mice. Seventy-five percent of hemizygous and 100% of homozygous transgenic males developed prostate tumors, suggesting a T Ag dosage effect. Biochemical characterization of advanced tumors revealed markers of both neuroendocrine and epithelial phenotypes; markers of terminal differentiation are lost early in tumorigenesis. Tumor suppressor genes (p53 and Rb), normally bound to T Ag, were up-regulated; bcl-2 proto-oncogene, which prevents apoptosis, was slightly up-regulated. Myc, a stimulus to cell cycle progression, was unchanged. We propose the Ggamma/T-15 transgenic line as a model of highly aggressive androgen-independent metastatic prostate carcinoma with features similar to end-stage prostate cancer in humans.
ISSN:0008-5472
1538-7445