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- Title
p27 Kip1 inhibits HER2/neu-mediated cell growth and tumorigenesis.
- Authors
Yang, Heng-Yin; Shao, Ruping; Hung, Mien-Chie; Lee, Mong-Hong
- 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. Oncogene (2001) 20, 3695–3702.
- Subjects
PROTEIN-tyrosine kinases; ONCOGENES; MITOGENS; CARCINOGENESIS
- Publication
Oncogene, 2001, Vol 20, Issue 28, p3695
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1204472