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p27 Kip1 inhibits HER2/neu-mediated cell growth and tumorigenesis

Oncogene volume 20, pages 3695–3702 (2001)Cite this article

Abstract

HER2/neu, a receptor tyrosine kinase oncogene, promotes mitogenic growth and transformation of cancer cells. We previously identified that its oncogenic signals down-regulate the cyclin-dependent kinase inhibitor p27 Kip1, which is defined as a haplo-insufficient tumor suppressor. Here, we applied the human p27 gene as a novel anticancer agent for HER2/neu-overexpressing cells under the control of a tetracycline (tet)-regulated gene expression system. Overexpression of p27 inhibits HER2/neu-activated CDK2 activity, cell proliferation, and transformation. Most significantly for clinical application, p27 expression in HER2/neu-overexpressing cells can be regulated in vivo and reduce the tumor volume in a tumor model. The findings demonstrate the applicability of employing p27 in HER2/neu-associated cancer gene therapy.

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Acknowledgements

We wish to thank HX Zhang and Amy Wang for technique help. This work was supported by the William McGowan Charitable foundation and Susan Komen Breast Cancer Foundation. H-Y Yang is a recipient of postdoctoral fellowship from DOD army breast cancer research program (DAMD17-98-1-8243). M-H Lee is a recipient of Flemin and Davenport research award.

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Authors and Affiliations

  1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Heng-Yin Yang, Ruping Shao, Mien-Chie Hung & Mong-Hong Lee

  2. Breast Cancer Research Program, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Mien-Chie Hung & Mong-Hong Lee

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  1. Heng-Yin Yang
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  2. Ruping Shao
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  3. Mien-Chie Hung
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  4. Mong-Hong Lee
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Yang, HY., Shao, R., Hung, MC. et al. p27 Kip1 inhibits HER2/neu-mediated cell growth and tumorigenesis. Oncogene 20, 3695–3702 (2001). https://doi.org/10.1038/sj.onc.1204472

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