A study published in *Nature* (2005) investigates the role of p53-dependent cellular senescence in suppressing tumorigenesis caused by Pten loss in the prostate. The research shows that while complete Pten inactivation in the prostate leads to nonlethal invasive prostate cancer after a long latency, the combined inactivation of Pten and Trp53 results in invasive prostate cancer as early as two weeks after puberty and is invariably lethal by 7 months of age. This indicates that p53-dependent cellular senescence is crucial for preventing tumorigenesis in Pten-deficient cells. Acute Pten inactivation induces growth arrest through the p53-dependent senescence pathway, which can be reversed by Trp53 loss. The study also found evidence of cellular senescence in early-stage human prostate cancer. The findings support a model where p53 acts as a critical safeguard for Pten-deficient tumors. The research highlights the importance of cellular senescence in restricting tumorigenesis in vivo and suggests that therapies targeting p53 activation could be beneficial for PTEN-deficient prostate cancer. The study used mouse models to demonstrate that Pten and Trp53 have a reciprocal relationship, with Pten protecting p53 and p53 enhancing Pten transcription. The results emphasize the cooperative role of these tumor suppressors in preventing cancer progression. The study also shows that the loss of Trp53 accelerates tumor progression in Pten-deficient tumors, indicating that p53 is essential for tumor suppression. The findings have therapeutic implications, suggesting that drugs that activate p53 could be effective in treating PTEN-deficient prostate cancer. The study provides insights into the molecular mechanisms underlying the interaction between Pten and p53 in prostate cancer and highlights the importance of cellular senescence in tumor suppression.A study published in *Nature* (2005) investigates the role of p53-dependent cellular senescence in suppressing tumorigenesis caused by Pten loss in the prostate. The research shows that while complete Pten inactivation in the prostate leads to nonlethal invasive prostate cancer after a long latency, the combined inactivation of Pten and Trp53 results in invasive prostate cancer as early as two weeks after puberty and is invariably lethal by 7 months of age. This indicates that p53-dependent cellular senescence is crucial for preventing tumorigenesis in Pten-deficient cells. Acute Pten inactivation induces growth arrest through the p53-dependent senescence pathway, which can be reversed by Trp53 loss. The study also found evidence of cellular senescence in early-stage human prostate cancer. The findings support a model where p53 acts as a critical safeguard for Pten-deficient tumors. The research highlights the importance of cellular senescence in restricting tumorigenesis in vivo and suggests that therapies targeting p53 activation could be beneficial for PTEN-deficient prostate cancer. The study used mouse models to demonstrate that Pten and Trp53 have a reciprocal relationship, with Pten protecting p53 and p53 enhancing Pten transcription. The results emphasize the cooperative role of these tumor suppressors in preventing cancer progression. The study also shows that the loss of Trp53 accelerates tumor progression in Pten-deficient tumors, indicating that p53 is essential for tumor suppression. The findings have therapeutic implications, suggesting that drugs that activate p53 could be effective in treating PTEN-deficient prostate cancer. The study provides insights into the molecular mechanisms underlying the interaction between Pten and p53 in prostate cancer and highlights the importance of cellular senescence in tumor suppression.