| Literature DB >> 18691549 |
Pradip K Majumder1, Chiara Grisanzio, Fionnuala O'Connell, Marc Barry, Joseph M Brito, Qing Xu, Isil Guney, Raanan Berger, Paula Herman, Rachel Bikoff, Giuseppe Fedele, Won-Ki Baek, Shunyou Wang, Katharine Ellwood-Yen, Hong Wu, Charles L Sawyers, Sabina Signoretti, William C Hahn, Massimo Loda, William R Sellers.
Abstract
Transgenic expression of activated AKT1 in the murine prostate induces prostatic intraepithelial neoplasia (PIN) that does not progress to invasive prostate cancer (CaP). In luminal epithelial cells of Akt-driven PIN, we show the concomitant induction of p27(Kip1) and senescence. Genetic ablation of p27(Kip1) led to downregulation of senescence markers and progression to cancer. In humans, p27(Kip1) and senescence markers were elevated in PIN not associated with CaP but were decreased or absent, respectively, in cancer-associated PIN and in CaP. Importantly, p27(Kip1) upregulation in mouse and human in situ lesions did not depend upon mTOR or Akt activation but was instead specifically associated with alterations in cell polarity, architecture, and adhesion molecules. These data suggest that a p27(Kip1)-driven checkpoint limits progression of PIN to CaP.Entities:
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Year: 2008 PMID： 18691549 PMCID： PMC2583442 DOI： 10.1016/j.ccr.2008.06.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743