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Impaired prostate tumorigenesis in Egr1-deficient mice

Nature Medicine volume 7, pages 101–107 (2001)Cite this article

Abstract

The transcription factor, early growth response protein 1 (EGR1), is overexpressed in a majority of human prostate cancers and is implicated in the regulation of several genes important for prostate tumor progression. Here we have assessed the effect of Egr1 deficiency on tumor development in two transgenic mouse models of prostate cancer (CR2-T-Ag and TRAMP). Using a combination of high-resolution magnetic resonance imaging and histopathological and survival analyses, we show that tumor progression was significantly impaired in Egr1−/− mice. Tumor initiation and tumor growth rate were not affected by the lack of Egr1; however, Egr1 deficiency significantly delayed the progression from prostatic intra-epithelial neoplasia to invasive carcinoma. These results indicate a unique role for Egr1 in regulating the transition from localized, carcinoma in situ to invasive carcinoma.

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Figure 1: Egr1 overexpression and loss of Nab2 expression in prostate tumors from CR2-T-Ag transgenic mice.
Figure 2: Kaplan-Meier survival analysis of Egr1-deficient CR2-T-Ag mice.
Figure 3: MRI analysis of tumor incidence and growth rate in transgenic mice.
Figure 4: Analysis of tumor initiation in transgenic mice.
Figure 5: Altered patterns of gene expression in CR2-T-Ag/Egr1−/− tumors.
Figure 6: Nab2 represses Egr1-mediated gene activation in prostate carcinoma cells.
Figure 7: Lack of Egr1 impairs tumorigenesis in the TRAMP model of prostate cancer.

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Acknowledgements

We thank N. Greenberg for TRAMP mice and G. Gavrilina , T. Gorodinsky, S. Audrain and C. Bollinger for technical assistance. This work was supported by NIH grants 5 P01 CA49712-08 (J.M.), R24 CA83060 (J.J.A.H.)and by grants from The Association for the Cure of Cancer of the Prostate (J.M.). S.A.A. was supported by NIH grants 5 T32CA09547-13 and 1KO8CA8790101.

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Authors and Affiliations

  1. Department of Pathology, Washington University, Box 8118, 660 S Euclid Avenue, St. Louis, 63119, Missouri, USA

    Sarki A. Abdulkadir, Zhican Qu, Thomas J. Peters, Peter A. Humphrey & Jeffrey Milbrandt

  2. Departments of Molecular Biology and Pharmacology, Washington University, Box 8118, 660 S Euclid Avenue, St. Louis, 63119, Missouri, USA

    Emily Garabedian & Jeffrey I. Gordon

  3. Department of Chemistry, Washington University, Box 8118, 660 S Euclid Avenue, St. Louis, 63119, Missouri, USA

    Sheng-Kwei Song & Joseph J.H. Ackerman

  4. Department of Comparative Biosciences, University of Wisconsin, Madison, 53706, Wisconsin, USA

    John Svaren

  5. Division of Urologic Surgery, Washington University School of Medicine,

    Joseph M. Carbone, Cathy K. Naughton & William J. Catalona

  6. Departments of Medicine and Radiology, Washington University School of Medicine,

    Joseph J.H. Ackerman

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  1. Sarki A. Abdulkadir
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Correspondence to Jeffrey Milbrandt.

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Abdulkadir, S., Qu, Z., Garabedian, E. et al. Impaired prostate tumorigenesis in Egr1-deficient mice. Nat Med 7, 101–107 (2001). https://doi.org/10.1038/83231

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