A team of researchers, led by Pier Paolo Pandolfi, at Beth Israel Deaconess Medical Center, Boston, has identified a new type of cellular senescence (i.e., irreversible arrest of cell growth) and determined a way to enhance it to suppress prostate tumor development and growth in mice.
Previous work by Pandolfi and colleagues determined that inactivation of the protein Pten leads to a senescence response that opposes tumorigenesis.
In this study, Pten-loss-induced cellular senescence (PICS) was found to be distinct from another form of cellular senescence known as oncogene-induced senescence in that it did not cause cellular proliferation and DNA damage. This was important because these two consequences of oncogene-induced senescence mean that enhancing this process for the treatment of cancer is not a viable option.
As pharmacological inhibition of PTEN was found to drive senescence and inhibit tumor development and growth in vivo in a human xenograft model of prostate cancer, the authors suggest that enhancing PICS might provide a new approach for cancer prevention and therapy.
The research appears in the Journal of Clinical Investigation.
- Andrea Alimonti, Caterina Nardella, Zhenbang Chen, John G. Clohessy, Arkaitz Carracedo, Lloyd C. Trotman, Ke Cheng, Shohreh Varmeh, Sara C. Kozma, George Thomas, Erika Rosivatz, Rudiger Woscholski, Francesco Cognetti, Howard I. Scher and Pier Paolo Pandolfi. A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI40535
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