PMID- 20392999
OWN - NLM
STAT- MEDLINE
DCOM- 20100518
LR  - 20211203
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 30
IP  - 3
DP  - 2010 Mar
TI  - Rapamycin-mediated FOXO1 inactivation reduces the anticancer efficacy of 
      rapamycin.
PG  - 799-804
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors such as rapamycin 
      have shown modest effects in cancer therapy due in part to the removal of a 
      negative feedback loop leading to the activation of the phosphatidylinositol 
      3-kinase/Akt (PI3K/Akt) signaling pathway. In this report, we have investigated 
      the role of FOXO1, a downstream substrate of the PI3K/Akt pathway in the 
      anticancer efficacy of rapamycin. MATERIALS AND METHODS: Colon cancer cells were 
      treated with rapamycin and FOXO1 phosphorylation was determined by Western blot. 
      Colon cancer cells transfected with a constitutively active mutant of FOXO1 or a 
      control plasmid were treated with rapamycin and the antiproliferative efficacy of 
      rapamycin was monitored. RESULTS: Rapamycin induced the phosphorylation of FOXO1 
      as well as its translocation from the nucleus to the cytoplasm, leading to FOXO1 
      inactivation. The expression of an active mutant of FOXO1 in colon cancer cells 
      potentiated the antiproliferative efficacy of rapamycin in vitro and its 
      antitumor efficacy in vivo. CONCLUSION: Taken together these results show that 
      rapamycin-induced FOXO1 inactivation reduces the antitumor efficacy of rapamycin.
FAU - Abdelnour-Berchtold, Etienne
AU  - Abdelnour-Berchtold E
AD  - Department of Visceral Surgery, University Hospital of Lausanne, Pavillon 3/CHUV, 
      Av de Beaumont, 1011 Lausanne, Switzerland.
FAU - Cerantola, Yannick
AU  - Cerantola Y
FAU - Roulin, Didier
AU  - Roulin D
FAU - Dormond-Meuwly, Anne
AU  - Dormond-Meuwly A
FAU - Demartines, Nicolas
AU  - Demartines N
FAU - Dormond, Olivier
AU  - Dormond O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/*pharmacology
MH  - Cell Growth Processes/drug effects
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/*drug therapy/genetics/metabolism/pathology
MH  - Female
MH  - Forkhead Box Protein O1
MH  - Forkhead Transcription Factors/*antagonists & 
      inhibitors/biosynthesis/genetics/metabolism
MH  - HT29 Cells
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Mice, Nude
MH  - Multiprotein Complexes
MH  - Proteins
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/antagonists & inhibitors/metabolism
MH  - Transfection
MH  - Xenograft Model Antitumor Assays
EDAT- 2010/04/16 06:00
MHDA- 2010/05/19 06:00
CRDT- 2010/04/16 06:00
PHST- 2010/04/16 06:00 [entrez]
PHST- 2010/04/16 06:00 [pubmed]
PHST- 2010/05/19 06:00 [medline]
AID - 30/3/799 [pii]
PST - ppublish
SO  - Anticancer Res. 2010 Mar;30(3):799-804.