Induction of apoptosis in p16INK4A mutant cell lines by adenovirus-mediated overexpression of p16INK4A protein.
- Resource Type
- Article
- Authors
- Kim, M; Katayose, Y; Rojanala, L; Shah, S; Sgagias, M; Jang, L; Jung, Y-J; Lee, S-H; Hwang, S-G; Cowan, K H
- Source
- Cell Death & Differentiation. Aug2000, Vol. 7 Issue 8, p706. 6p.
- Subject
- *TUMOR suppressor genes
*CELL cycle
- Language
- ISSN
- 1350-9047
The tumor suppressor gene p16[sup INK4A] is a cyclin-dependent kinase inhibitor (CDKI) and an important cell cycle regulator. We have previously constructed a recombinant adenovirus which expresses p16 (Adp16) and shown that infection in a variety of human tumor cell lines with this recombinant virus results in high levels of p16[sup INK4A] protein expression resulting in cell cycle arrest and loss of cyclin-cdk activity. Furthermore, adenoviral-mediated overexpression of wild-type p16[sup INK4A] is more toxic in cancer cells which express mutant forms of p16[sup 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[sup 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. [ABSTRACT FROM AUTHOR]