PMID- 17213801
OWN - NLM
STAT- MEDLINE
DCOM- 20070816
LR  - 20211203
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 26
IP  - 32
DP  - 2007 Jul 12
TI  - A gene transcription signature of the Akt/mTOR pathway in clinical breast tumors.
PG  - 4648-55
AB  - The Akt pathway is commonly deregulated in many cancers. Clinical trials are 
      currently underway to test the effectiveness of breast cancer treatment by 
      inhibition of various Akt pathway intermediates. A set of genes induced by Akt in 
      a transgenic mouse model, a subset of which were sensitive to mammalian target of 
      rapamycin (mTOR) inhibitor RAD001, was examined in five public gene expression 
      profile data sets of clinical breast tumor specimens (representing >1000 
      different samples in all). In each of the clinical data sets, the Akt mouse model 
      genes as a group were significantly overexpressed in human tumors having high 
      levels of AKT1 mRNA. The subset of genes both upregulated by Akt and dependent on 
      mTOR activity were associated with estrogen receptor-negative status, higher 
      grade, increasing tumor size and poor prognosis in multiple patient cohorts; 
      these associations were either not present or not as strong for the Akt-induced, 
      mTOR-independent genes or for AKT1 expression alone. The genes shown here to be 
      relevant to Akt-mTOR both experimentally and pathologically have the potential 
      for use in a molecular diagnostic to determine which patients should receive mTOR 
      antagonist treatment.
FAU - Creighton, C J
AU  - Creighton CJ
AD  - Department of Medicine, Dan L Duncan Cancer Center, Division of Biostatistics, 
      Baylor College of Medicine, Houston, TX 77030, USA. creighto@bcm.tmc.edu
LA  - eng
PT  - Journal Article
DEP - 20070108
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/genetics/*pathology
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - *Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - *Genes, Neoplasm
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Prognosis
MH  - Protein Kinases/genetics/*physiology
MH  - Proto-Oncogene Proteins c-akt/genetics/*physiology
MH  - RNA, Messenger/analysis/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Transcription, Genetic
EDAT- 2007/01/11 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/01/11 09:00
PHST- 2007/01/11 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/01/11 09:00 [entrez]
AID - 1210245 [pii]
AID - 10.1038/sj.onc.1210245 [doi]
PST - ppublish
SO  - Oncogene. 2007 Jul 12;26(32):4648-55. doi: 10.1038/sj.onc.1210245. Epub 2007 Jan 
      8.