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

39 Scopus citations

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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