Wild-type p53 triggers a rapid senescence program in human tumor cells lacking functional p53

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Title
Wild-type p53 triggers a rapid senescence program in human tumor cells lacking functional p53
Author(s)
M M Sugrue; Deug Y Shin; Sam W Lee; S A Aaronson
Bibliographic Citation
Proceedings of National Academy of Sciences of United States of America, vol. 94, no. 18, pp. 9648-9653
Publication Year
1997
Abstract
The p53 tumor suppressor gene has been shown to play an important role in determining cell fate. Overexpression of wild-type p53 in tumor cells has been shown to lead to growth arrest or apoptosis. Previous studies in fibroblasts have provided indirect evidence for a link between p53 and senescence. Here we show, using an inducible p53 expression system, that wild-type p53 overexpression in EJ bladder carcinoma cells, which have lost functional p53, triggers the rapid onset of G1 and G2/M growth arrest associated with p21 upregulation and repression of mitotic cyclins (cyclin A and B) and cdc2. Growth arrest in response to p53 induction became irreversible within 48-72 h, with cells exhibiting morphological features as well as specific biochemical and ultrastructural markers of the senescent phenotype. These findings provide direct evidence that p53 overexpression can activate the rapid onset of senescence in tumor cells.
Keyword
EJTumor suppression
ISSN
0027-8424
Publisher
Natl Acad Sciences
DOI
http://dx.doi.org/10.1073/pnas.94.18.9648
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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