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Oncogene. 2001 Jun 21;20(28):3695-702.

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

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

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.

PMID:
11439332
DOI:
10.1038/sj.onc.1204472
[Indexed for MEDLINE]
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