Genomic instability-based transgenic models of prostate cancer

Christina Voelkel-Johnson, Dale J. Voeks, Norman M. Greenberg, Roberto Barrios, Frideriki Maggouta, David T. Kurtz, David A. Schwartz, Gina M. Keller, Thomas Papenbrock, Gary Clawson, James S. Norris

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

To develop animal models that represent the broad spectrum of human prostate cancer, we created transgenic mice with targeted prostate-specific expression of two genes (EcoRI and c-fos) implicated in the induction of genomic instability. Expression of the transgenes was restricted to prostate epithelial cells by coupling them to the tissuespecific, hormonally regulated probasin promoter (PB). The effects of transgene expression were examined histologically in prostate sections at time points taken from 4 to 24 months of age. The progressive presence of regions of mild-to-severe hyperplasia, low- and high-grade prostatic intra-epithelial neoplasia, and well-differentiated adenocarcinoma was observed in both PBEcoRI lines but no significant pathology was detected in the PBfos line. Prostate tissue of PBEcoRI mice was examined for expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 at multiple time points. Although p53 does not appear to be mutated, levels of PCNA and Ki67 are elevated and correlate with the severity of the prostatic lesions. Overall, pre-neoplastic and neoplastic stages represented in the PBEcoRI model showed similarity to corresponding early stages of the human disease. This genomic instability-based model will be used to study the mechanisms involved in the early stages of prostate carcinogenesis and to investigate the nature of subsequent events necessary for the progression to advanced disease.

Original languageEnglish (US)
Pages (from-to)1623-1627
Number of pages5
JournalCarcinogenesis
Volume21
Issue number8
DOIs
StatePublished - Jan 1 2000

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Genomic Instability
Prostate
Prostatic Neoplasms
Ki-67 Antigen
Proliferating Cell Nuclear Antigen
Transgenes
fos Genes
Transgenic Mice
Hyperplasia
Carcinogenesis
Adenocarcinoma
Animal Models
Epithelial Cells
Pathology
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Voelkel-Johnson, C., Voeks, D. J., Greenberg, N. M., Barrios, R., Maggouta, F., Kurtz, D. T., ... Norris, J. S. (2000). Genomic instability-based transgenic models of prostate cancer. Carcinogenesis, 21(8), 1623-1627. https://doi.org/10.1093/carcin/21.5.623
Voelkel-Johnson, Christina ; Voeks, Dale J. ; Greenberg, Norman M. ; Barrios, Roberto ; Maggouta, Frideriki ; Kurtz, David T. ; Schwartz, David A. ; Keller, Gina M. ; Papenbrock, Thomas ; Clawson, Gary ; Norris, James S. / Genomic instability-based transgenic models of prostate cancer. In: Carcinogenesis. 2000 ; Vol. 21, No. 8. pp. 1623-1627.
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Voelkel-Johnson, C, Voeks, DJ, Greenberg, NM, Barrios, R, Maggouta, F, Kurtz, DT, Schwartz, DA, Keller, GM, Papenbrock, T, Clawson, G & Norris, JS 2000, 'Genomic instability-based transgenic models of prostate cancer', Carcinogenesis, vol. 21, no. 8, pp. 1623-1627. https://doi.org/10.1093/carcin/21.5.623

Genomic instability-based transgenic models of prostate cancer. / Voelkel-Johnson, Christina; Voeks, Dale J.; Greenberg, Norman M.; Barrios, Roberto; Maggouta, Frideriki; Kurtz, David T.; Schwartz, David A.; Keller, Gina M.; Papenbrock, Thomas; Clawson, Gary; Norris, James S.

In: Carcinogenesis, Vol. 21, No. 8, 01.01.2000, p. 1623-1627.

Research output: Contribution to journalArticle

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Voelkel-Johnson C, Voeks DJ, Greenberg NM, Barrios R, Maggouta F, Kurtz DT et al. Genomic instability-based transgenic models of prostate cancer. Carcinogenesis. 2000 Jan 1;21(8):1623-1627. https://doi.org/10.1093/carcin/21.5.623