|
| | | | |
| | | |
| Stat |
Members: 3645
Articles: 2'506'133
Articles rated: 2609
26 April 2024 |
|
| | | | |
|
Article overview
| |
|
|
Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis | | Zhenbang Chen
; Lloyd C Trotman
; David Shaffer
; Hui-Kuan Lin
; Zohar A Dotan
; Masaru Niki
; Jason A Koutcher
; Howard I Scher
; Thomas Ludwig
; William Gerald
; Carlos Cordon-Cardo
; Pier Paolo Pandolfi
; | | Date: |
4 Aug 2005 | | Journal: | Nature, 436 (7051), 725-30 | | Abstract: | Cellular senescence has been theorized to oppose neoplastic transformation triggered by activation of oncogenic pathways in vitro, but the relevance of senescence in vivo has not been established. The PTEN and p53 tumour suppressors are among the most commonly inactivated or mutated genes in human cancer including prostate cancer. Although they are functionally distinct, reciprocal cooperation has been proposed, as PTEN is thought to regulate p53 stability, and p53 to enhance PTEN transcription. Here we show that conditional inactivation of Trp53 in the mouse prostate fails to produce a tumour phenotype, whereas complete Pten inactivation in the prostate triggers non-lethal invasive prostate cancer after long latency. Strikingly, combined inactivation of Pten and Trp53 elicits invasive prostate cancer as early as 2 weeks after puberty and is invariably lethal by 7 months of age. Importantly, acute Pten inactivation induces growth arrest through the p53-dependent cellular senescence pathway both in vitro and in vivo, which can be fully rescued by combined loss of Trp53. Furthermore, we detected evidence of cellular senescence in specimens from early-stage human prostate cancer. Our results demonstrate the relevance of cellular senescence in restricting tumorigenesis in vivo and support a model for cooperative tumour suppression in which p53 is an essential failsafe protein of Pten-deficient tumours. | | Source: | PubMed, pmid16079851 doi: 10.1038/nature03918 | | Services: | Forum | Review | Favorites | |
|
|
No review found.
Did you like this article?
Note: answers to reviews or questions about the article must be posted in the forum section.
Authors are not allowed to review their own article. They can use the forum section.
browser Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)
|
| |
|
|
|
|
News, job offers and information for researchers and scientists:
| |
REGISTER