Open AccessPten null prostate tumorigenesis and AKT activation are blocked by targeted knockout of ER chaperone GRP78/BiP in prostate epithelium
Author(s) -
Yong Fu,
Shiuan Wey,
Miao Wang,
Risheng Ye,
ChunPeng Liao,
Pradip RoyBurman,
Amy S. Lee
Publication year - 2008
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0807691105
Subject(s) - pten , prostate cancer , prostate , protein kinase b , cancer research , carcinogenesis , pi3k/akt/mtor pathway , tramp , biology , knockout mouse , epithelium , conditional gene knockout , gene knockdown , cancer , pathology , medicine , apoptosis , phosphorylation , signal transduction , microbiology and biotechnology , receptor , gene , biochemistry , phenotype
GRP78/BiP has recently emerged as a novel biomarker for aggressive prostate cancer. Here, we report that homozygous deletion ofGrp78 specifically in mouse prostate epithelium suppresses prostate tumorigenesis without affecting postnatal prostate development and growth. Mouse prostates with double conditional knockout ofGrp78 andPten exhibit normal histology and cytology, in contrast to the invasive adenocarcinoma in mouse prostates withPten inactivation. AKT activation inPten null prostate epithelium is inhibited byGrp78 homozygous deletion, corresponding with suppression of AKT phosphorylation by GRP78 knockdown in prostate cancer cell line. Thus, inactivation of GRP78 may represent a previously undescribed approach to stop prostate cancer and potentially other cancers resulting from the loss of PTEN tumor suppression and/or activation of the oncogenic AKT.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom