PMID- 15592522
OWN - NLM
STAT- MEDLINE
DCOM- 20050314
LR  - 20191210
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 24
IP  - 7
DP  - 2005 Feb 10
TI  - REDD1 integrates hypoxia-mediated survival signaling downstream of 
      phosphatidylinositol 3-kinase.
PG  - 1138-49
AB  - Cancer cells frequently evade apoptosis during tumorigenesis by acquiring 
      mutations in apoptotic regulators. Chronic activation of the PI 3-kinase-Akt 
      pathway through loss of the tumor suppressor PTEN is one mechanism by which these 
      cells can gain increased protection against apoptosis. We report here that REDD1 
      (RTP801) can act as a transcriptional downstream target of PI 3-kinase signaling 
      in human prostate cancer cells (PC-3). REDD1 expression is markedly reduced in 
      PC-3 cells treated with LY294002 (LY) or Rapamycin and strongly induced under 
      hypoxic conditions in a hypoxia-inducible factor-1 (HIF-1)-dependent manner. Loss 
      of function studies employing antisense molecules or RNA interference indicate 
      that REDD1 is essential for invasive growth of prostate cancer cells in vitro and 
      in vivo. Reduced REDD1 levels can sensitize cells towards apoptosis, whereas 
      elevated levels of REDD1 induced by hypoxia or overexpression desensitize cells 
      to apoptotic stimuli. Taken together our data designate REDD1 as a novel target 
      for therapeutic intervention in prostate cancer.
FAU - Schwarzer, Rolf
AU  - Schwarzer R
AD  - Atugen AG, Otto Warburg Haus (Nr. 80), Robert-Roessle-Strasse 10, 13125 Berlin, 
      Germany.
FAU - Tondera, Daniel
AU  - Tondera D
FAU - Arnold, Wolfgang
AU  - Arnold W
FAU - Giese, Klaus
AU  - Giese K
FAU - Klippel, Anke
AU  - Klippel A
FAU - Kaufmann, Jorg
AU  - Kaufmann J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Chromones)
RN  - 0 (DDIT4 protein, human)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (RNA, Antisense)
RN  - 0 (Transcription Factors)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 3G0H8C9362 (Cobalt)
RN  - EVS87XF13W (cobaltous chloride)
RN  - W36ZG6FT64 (Sirolimus)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
MH  - Apoptosis
MH  - Cell Hypoxia
MH  - Cell Line, Tumor
MH  - Chromones/pharmacology
MH  - Cobalt/pharmacology
MH  - Dimethyl Sulfoxide/pharmacology
MH  - Gene Expression/genetics
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Male
MH  - Morpholines/pharmacology
MH  - Neoplasm Invasiveness/genetics
MH  - Phosphatidylinositol 3-Kinases/genetics/*physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Prostatic Neoplasms/genetics/immunology/*metabolism
MH  - RNA, Antisense/genetics
MH  - Signal Transduction
MH  - Sirolimus/pharmacology
MH  - Transcription Factors/analysis/genetics/*physiology
MH  - Up-Regulation
EDAT- 2004/12/14 09:00
MHDA- 2005/03/15 09:00
CRDT- 2004/12/14 09:00
PHST- 2004/12/14 09:00 [pubmed]
PHST- 2005/03/15 09:00 [medline]
PHST- 2004/12/14 09:00 [entrez]
AID - 1208236 [pii]
AID - 10.1038/sj.onc.1208236 [doi]
PST - ppublish
SO  - Oncogene. 2005 Feb 10;24(7):1138-49. doi: 10.1038/sj.onc.1208236.