Reference SummaryPerez-Stable C, Lab Invest 1996 Feb;74(2):363-73

Title

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

Authors

 Perez-Stable C; Altman NH; Brown J; Harbison M; Cray C; Roos BA

Journal

 Lab Invest

Volume

 74

Issue

 2

Year

 1996

Pages

 363-73

Abstract

 Targeted oncogenesis in transgenic mice has unexpectedly produced predictable tissue-specific tumors. We previously showed that hybrid gene constructs of the human fetal G gamma- or mouse embryonic beta h1-globin promoter linked to the viral simian virus 40 T antigen (G gamma/T and beta h1/T) expressed appropriately in embryonic erythroid tissue, with some unexpected expression elsewhere. Tumors arising in the G gamma/T and beta h1/T transgenic mice were identified by histology, electron microscopy, cell culture, and RNase protection analyses. In one G gamma/T transgenic line, males developed prostate tumors that showed mixed neuroendocrine and epithelial cell features, whereas females developed adrenocortical tumors. In several other G gamma/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, beta h1/T transgenic mice developed only choroid plexus tumors. Transient transfection assays in prostate and adrenocortical tumor-derived cell lines showed that the G gamma-globin promoter is 7-to 10-fold more active than the beta h1-globin promoter. Activity of 5' G gamma-globin promoter-deletion DNA plasmids was analyzed by transient transfection in a variety of human prostate cancer cell lines. The G gamma-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 G gamma/T transgenic lines apparently results from cryptic positive DNA cis elements active in prostate and adrenocortical cells. Because G gamma-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.

Links

 J:52340 – MGI References
8780156 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6;CB-Tg(Ggamma-T)15Cps Expression of the "Ggamma-T" transgene was reported to not be detected in the adrenal glands, liver, heart, lungs, and erythrocytes of these mice.
Expression of the "Ggamma-T" transgene was reported to not be detected in the testis, prostate gland, adrenal glands, liver, heart, lungs, brain, spleen, and erythrocytes of these mice.
The "Ggamma-T" transgene was reported to be expressed in the ovaries of these mice.
The "Ggamma-T" transgene was reported to be expressed in the prostate gland of these mice.
B6;CB-Tg(Ggamma-T)21Cps Expression of the "Ggamma-T" transgene was reported to not be detected in the prostate gland, testis, adrenal glands, liver, heart, lungs, erythrocytes, and adipose tissue (taken from the interscapular shoulder area) of these mice.
The "Ggamma-T" transgene was reported to be expressed in the adipose tissue (taken from near the heart) of these mice.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6;CB-Tg(Ggamma-T)21Cps Adipose tissue - Brown hibernoma Adipose tissue - Brown

75
B6;CB-Tg(Ggamma-T)21Cps Adipose tissue - Brown hibernoma Adrenal gland

40
B6;CB-Tg(Ggamma-T)21Cps Adipose tissue - Brown hibernoma Heart

40
B6;CB-Tg(Ggamma-T)20Cps Adipose tissue - Brown hibernoma Adipose tissue - Brown

100
B6;CB-Tg(Ggamma-T)2Cps Adipose tissue - Brown hibernoma Adrenal gland

5
B6;CB-Tg(Ggamma-T)2Cps Adipose tissue - Brown hibernoma Heart

5
B6;CB-Tg(Ggamma-T)15Cps Adrenal gland - Cortex tumor Adrenal gland - Cortex

50
B6;CB-Tg(betah1-T)13Cps CNS - Brain - Choroid plexus tumor CNS - Brain - Choroid plexus

50
B6;CB-Tg(betah1-T)5Cps CNS - Brain - Choroid plexus tumor CNS - Brain - Choroid plexus

20
B6;CB-Tg(betah1-T)37Cps CNS - Brain - Choroid plexus tumor CNS - Brain - Choroid plexus

10
B6;CB-Tg(Ggamma-T)15Cps Prostate gland tumor Prostate gland

50
B6;CB-Tg(Ggamma-T)21Cps Prostate gland tumor Prostate gland

20
B6;CB-Tg(betah1-T)3Cps (Unspecified organ) tumor (Unspecified organ)

0