Abstract
The tumor suppressor gene p16(INK4A) is a cyclin-dependent kinase inhibitor (CDKI) and an important cell cycle regulator. We have previously constructed a recombinant adenovirus which expresses p16 (Adp 16) and shown that infection in a variety of human tumor cell lines with this recombinant virus results in high levels of p16(INK4A) protein expression resulting in cell cycle arrest and loss of cyclin-cdk activity. Furthermore, adenoviral-mediated overexpression of wild-type p16(INK4A) is more toxic in cancer cells which express mutant forms of p16(INK4A) compared to cancer cell lines containing endogenous wild-type p16. TUNEL assay and DAPI staining following infection of MDA-MB 231 breast cancer cells with Adp16 indicate that p16(INK4A)-mediated cytotoxicity was associated with apoptosis. This is supported by studies demonstrating a decrease in cpp32 and cyclinB1 protein levels and induction of poly (ADP-ribose) polymerase (PARP) cleavage following infection of MDA-MB-231 cells with Adp16. These results suggest that gene therapy using Adp16 may be a promising treatment option for human cancers containing alterations in p16 expression.
Original language | English (US) |
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Pages (from-to) | 706-711 |
Number of pages | 6 |
Journal | Cell Death and Differentiation |
Volume | 7 |
Issue number | 8 |
DOIs | |
State | Published - 2000 |
Keywords
- Adenovirus
- Apoptosis
- Gene therapy
- P16(INK4A)
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology