Open AccessSTAMP 2 increases oxidative stress and is critical for prostate cancer
Author(s) -
Jin Yang,
Wang Ling,
Qu Su,
Sheng Xia,
Kristian Alexandr,
Mælandsmo Gunhild M,
Pällmann Nora,
Yuca Erkan,
Tekedereli Ibrahim,
Gorgulu Kivanc,
Alpay Neslihan,
Sood Anil,
LopezBerestein Gabriel,
Fazli Ladan,
Rennie Paul,
Risberg Bjørn,
Wæhre Håkon,
Danielsen Håvard E,
Ozpolat Bulent,
Saatcioglu Fahri
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201404181
Subject(s) - gene silencing , gene knockdown , prostate cancer , cancer research , apoptosis , transcription factor , oxidative stress , prostate , messenger rna , chemistry , biology , microbiology and biotechnology , medicine , cancer , endocrinology , gene , biochemistry
The six transmembrane protein of prostate 2 ( STAMP 2) is an androgen‐regulated gene whose mRNA expression is increased in prostate cancer ( PC a). Here, we show that STAMP 2 protein expression is increased in human PC a compared with benign prostate that is also correlated with tumor grade and treatment response. We also show that STAMP 2 significantly increased reactive oxygen species ( ROS ) in PC a cells through its iron reductase activity which also depleted NADPH levels. Knockdown of STAMP 2 expression in PC a cells inhibited proliferation, colony formation, and anchorage‐independent growth, and significantly increased apoptosis. Furthermore, STAMP 2 effects were, at least in part, mediated by activating transcription factor 4 ( ATF 4), whose expression is regulated by ROS . Consistent with in vitro findings, silencing STAMP 2 significantly inhibited PC a xenograft growth in mice. Finally, therapeutic silencing of STAMP 2 by systemically administered nanoliposomal si RNA profoundly inhibited tumor growth in two established preclinical PC a models in mice. These data suggest that STAMP 2 is required for PC a progression and thus may serve as a novel therapeutic target.