Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 18 August 2009
Vol. 2, Issue 84, p. ra44
[DOI: 10.1126/scisignal.2000053]


Editor's Summary

Not Always a Tumor Suppressor
In most cases, cancer progression depends on multiple genetic insults. For example, in prostate, the complete loss of the gene that encodes the tumor suppressor Pten (phosphatase and tensin homolog deleted from chromosome 10) elicits a compensatory increase in the abundance of the tumor suppressor p53, which contributes to a cellular senescence response that inhibits cancer progression. Thus, in mouse prostate, loss of Pten alone leads to a nonlethal form of prostate cancer, whereas concomitant inactivation of the genes encoding both Pten and p53 leads to a rapidly lethal form of the disease. The tumor suppressor p19Arf is known for its role in inhibiting p53 degradation. Chen et al. found that, unexpectedly, loss of p19Arf failed to phenocopy the effect of p53 loss on the progression of mouse prostate cancer associated with loss of Pten. Rather, mice lacking both Pten and p19Arf retained a senescence response and showed a decrease in pre-neoplastic prostate lesions. Moreover, in both mouse prostate and mouse embryo fibroblasts, the increase in p53 elicited by loss of Pten was unaffected by loss of p19Arf. Thus, the authors conclude that p19Arf signals independently of p53 in prostate cancer associated with loss of Pten and does not play a tumor suppressor role in the prostate epithelium.

Citation: Z. Chen, A. Carracedo, H.-K. Lin, J. A. Koutcher, N. Behrendt, A. Egia, A. Alimonti, B. S. Carver, W. Gerald, J. Teruya-Feldstein, M. Loda, P. P. Pandolfi, Differential p53-Independent Outcomes of p19Arf Loss in Oncogenesis. Sci. Signal. 2, ra44 (2009).

Read the Full Text

Antagonistic TSC22D1 variants control BRAFE600-induced senescence.
C. Homig-Holzel, R. van Doorn, C. Vogel, M. Germann, M. G. Cecchini, E. Verdegaal, and D. S. Peeper (2011)
EMBO J. 30, 1753-1765
   Abstract »    Full Text »    PDF »
Molecular genetics of prostate cancer: new prospects for old challenges.
M. M. Shen and C. Abate-Shen (2010)
Genes & Dev. 24, 1967-2000
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882