Research ArticleCancer

Differential p53-Independent Outcomes of p19Arf Loss in Oncogenesis

Science Signaling  18 Aug 2009:
Vol. 2, Issue 84, pp. ra44
DOI: 10.1126/scisignal.2000053

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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.