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Pim1 kinase is required to maintain tumorigenicity in MYC-expressing prostate cancer cells

Oncogene volume 31, pages 1794–1803 (2012)Cite this article

Abstract

PIM1 kinase and MYC are commonly co-expressed in human prostate cancer and synergize to induce rapidly progressing prostate cancer in mouse models. Deficiency of the Pim kinase genes is well tolerated in vivo, suggesting that PIM1 inhibition might offer an attractive therapeutic modality for prostate cancer, particularly for MYC-expressing tumors. Here we examine the molecular consequences of Pim1 and MYC overexpression in the prostate as well as the effects of depleting Pim1 in prostate carcinoma cells with high levels of MYC. Overexpression of Pim1 in the mouse prostate induces several pro-tumorigenic genetic programs including cell cycle genes and Myc-regulated genes before the induction of any discernible pathology. Pim1 depletion by RNA interference in mouse and human prostate cancer cells decreased cellular proliferation, survival, Erk signaling and tumorigenicity even when MYC levels were not significantly altered. These results indicate that PIM1 may be necessary to maintain tumorigenicity, and further support efforts aimed at developing PIM1 inhibitors for prostate cancer therapy.

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Acknowledgements

We thank Drs Robert Matusik, Simon Hayward, Vito Quaranta, Xiuping Yu and Fritz Parl for helpful discussions. Micrographs were taken from Cell Imaging Core at Vanderbilt University Medical Center. This work was supported by Grant RO1CA123484 from the NCI to SAA. while DG is supported by R01CA152601 from the NCI and BC093803 from the DOD.

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Authors and Affiliations

  1. Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA

    J Wang, D Gius & S A Abdulkadir

  2. Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA

    P D Anderson, M Roh & S A Abdulkadir

  3. Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA

    W Luo

  4. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA

    D Gius

  5. Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    D Gius

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  1. J Wang
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Correspondence to S A Abdulkadir.

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The authors declare no conflict of interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Wang, J., Anderson, P., Luo, W. et al. Pim1 kinase is required to maintain tumorigenicity in MYC-expressing prostate cancer cells. Oncogene 31, 1794–1803 (2012). https://doi.org/10.1038/onc.2011.371

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  • DOI: https://doi.org/10.1038/onc.2011.371

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