p51/p63, a novel p53 homologue, potentiates p53 activity and is a human cancer gene therapy candidate

✍ Scribed by Reiko Kunisaki; Shuntaro Ikawa; Toyoki Maeda; Yukoh Nakazaki; Ryo Kurita; Masamitsu Harata; Yukinobu Shutoh; Yuang Sung Bai; Yasushi Soda; Tsuyoshi Tanabe; Taeko Dohi; Rie Kato; Yoji Ikawa; Shigetaka Asano; Kenzaburo Tani

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 551 KB
• Volume: 8
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.945

✦ Synopsis

Abstract

Background

p51 (p73L/p63/p40/KET), a recently isolated novel p53 homologue, binds to p53‐responsive elements to upregulate some p53 target genes and has been suggested to share partially overlapping functions with p53. p51 may be a promising candidate target molecule for anti‐cancer therapy.

Methods

In this study, we adenovirally transduced p51A cDNA into human lung, gastric and pancreatic cancer cells and analyzed the intracellular function of p51 in anti‐oncogenesis in vitro and in vivo.

Results

Overexpression of p51A revealed an anti‐proliferative effect in vitro in all the cancer cells examined in this study. The anchorage‐dependent and ‐independent cell growth of EBC1 cells carrying mutations in both p51 and p53 was suppressed and significant apoptosis following adenoviral transduction with p51 and/or p53 was seen. This growth suppression was cooperatively enhanced by the combined infection with adenoviral vectors encoding both p51 and p53. Furthermore, p51 activated several, but not all, p53‐inducible genes, indicating that the mechanisms controlling p51‐ and p53‐mediated tumor suppression differed.

Conclusions

Our observations indicate that, although p51 exhibited reduced anti‐oncogenetic effects compared with p53, it cooperatively enhanced the anti‐tumor effects of p53. Our results suggest that p51 functions as a tumor suppressor in human cancer cells in vitro and in vivo and may be useful as a potential tool for cancer gene therapy. Copyright © 2006 John Wiley & Sons, Ltd.