A Prostatic Intraepithelial Neoplasia-Dependent p27Kip1 Checkpoint Induces Senescence and Inhibits Cell Proliferation and Cancer Progression

Authors
Pradip K. MajumderChiara GrisanzioFionnuala O’ConnellMarc BarryJoseph M. BritoQing XuIsil GuneyRaanan BergerPaula HermanRachel BikoffGiuseppe FedeleWon-Ki BaekShunyou WangKatharine Ellwood-YenHong WuCharles L. SawyersSabina SignorettiWilliam C. HahnMassimo LodaWilliam R. Sellers
Department
Dept. of Microbiology (미생물학)
Issue Date
2008
Citation
Cancer Cell, Vol.14(2) : 146-155, 2008
ISSN
1535-6108
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 p27Kip1 and senescence. Genetic ablation of p27Kip1 led to downregulation of senescence markers and progression to cancer. In humans, p27Kip1 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, p27Kip1 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 p27Kip1-driven checkpoint limits progression of PIN to CaP. Author Keywords CELLCYCLE
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35285
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
Keimyung Author(s)
백원기
File in this Item
oak-aaa-00743.pdf(1.84 MB)Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE