Prostate, adrenocortical, and brown adipose tumors in fetal globin/T antigen transgenic mice

Carlos Perez-Stable, Norman H. Altman, John Brown, Margaret Harbison, Carolyn Cray, Bernard A. Roos

Research output: Contribution to journalArticle

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Abstract

Targeted oncogenesis in transgenic mice has unexpectedly produced predictable tissue-specific tumors. We previously showed that hybrid gene constructs of the human fetal Gγ- or mouse embryonic βh1-globin promoter linked to the viral simian virus 40 T antigen (Gγ/T and βh1/T) expressed appropriately in embryonic erythroid tissue, with some unexpected expression elsewhere. Tumors arising in the Gγ/T and βh1/T transgenic mice were identified by histology, electron microscopy, cell culture, and RNase protection analyses. In one Gγ/T transgenic line, males developed prostate tumors that showed mixed neuroendocrine and epithelial cell features, whereas females developed adrenocortical tumors. In several other Gγ/T lines, brown adipose tumors, or hibernomas, developed in the subcutaneous interscapular neck and shoulder area, as well as internally in the periadrenal and pericardial areas. Little or no expression of T antigen was detected in adult animals before visible tumor formation. In contrast, βh1/T transgenic mice developed only choroid plexus tumors. Transient transfection assays in prostate and adrenocortical tumor-derived cell lines showed that the Gγ- globin promoter is 7- to 10-fold more active than the βh1-globin promoter. Activity of 5' Gγ-globin promoter-deletion DNA plasmids was analyzed by transient transfection in a variety of human prostate cancer cell lines. The Gγ-globin promoter region between -140 and -201 also showed high activity in the androgen-independent human prostate cancer cell lines DU-145 and PPC-1, but low activity in the androgen-responsive human prostate cell line LNCaP. We conclude that tumor formation in the Gγ/T transgenic lines apparently results from cryptic positive DNA cis elements active in prostate and adrenocortical cells. Because Gγ-globin promoter activity is highest in embryonic tissue, tumors in adult transgenic mice may result from expression of T antigen in embryonic prostate, adrenal glands, and brown adipose tissue.

Original languageEnglish
Pages (from-to)363-373
Number of pages11
JournalLaboratory Investigation
Volume74
Issue number2
StatePublished - Feb 1 1996

Fingerprint

Globins
Viral Tumor Antigens
Transgenic Mice
Prostate
Neoplasms
Cell Line
Androgens
Transfection
Prostatic Neoplasms
Choroid Plexus Neoplasms
Neuroendocrine Cells
Brown Adipose Tissue
Simian virus 40
Lipoma
DNA
Ribonucleases
Adrenal Glands
Tumor Cell Line
Genetic Promoter Regions
Histology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Prostate, adrenocortical, and brown adipose tumors in fetal globin/T antigen transgenic mice. / Perez-Stable, Carlos; Altman, Norman H.; Brown, John; Harbison, Margaret; Cray, Carolyn; Roos, Bernard A.

In: Laboratory Investigation, Vol. 74, No. 2, 01.02.1996, p. 363-373.

Research output: Contribution to journalArticle

Perez-Stable, Carlos ; Altman, Norman H. ; Brown, John ; Harbison, Margaret ; Cray, Carolyn ; Roos, Bernard A. / Prostate, adrenocortical, and brown adipose tumors in fetal globin/T antigen transgenic mice. In: Laboratory Investigation. 1996 ; Vol. 74, No. 2. pp. 363-373.
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