Adenoviral Expression of the Cyclin-Dependent Kinase Inhibitor p27Kip1: a Strategy for Breast Cancer Gene Therapy

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Abstract
Cyclin-dependent kinase inhibitors play a critical role in regulating progression of the eukaryotic cell through the cell cycle by associating with protein complexes composed of cyclins and cyclin- dependent kinases and thus downmodulating the activity of the cyclindependent kinases ( 1 ) . Pathways involving cyclin-dependent kinase inhibitors are frequently disrupted in cancer cells, and this disruption leads to abnormal regulation of the cell cycle. Overexpression of cyclin-dependent kinase inhibitors leads to the arrest of cells at one of the checkpoints in the cell cycle ( 2 ) . Therefore, using cyclindependent kinase inhibitors for gene therapy of cancer is intuitively attractive because it has the potential to inhibit tumor growth ( 3 ) . Thus far, adenoviral vectors expressing the cyclin-dependent kinase inhibitors p16INK4A and p21waf1/cip1 have been evaluated in preclinical models for their suitability for gene therapy of cancer ( 3–9 ) .