PMID- 20133820
OWN - NLM
STAT- MEDLINE
DCOM- 20101214
LR  - 20211203
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 176
IP  - 4
DP  - 2010 Apr
TI  - Novel proteins regulated by mTOR in subependymal giant cell astrocytomas of 
      patients with tuberous sclerosis complex and new therapeutic implications.
PG  - 1878-90
LID - 10.2353/ajpath.2010.090950 [doi]
AB  - Subependymal giant cell astrocytomas (SEGAs) are rare brain tumors associated 
      with tuberous sclerosis complex (TSC), a disease caused by mutations in TSC1 or 
      TSC2, resulting in enhancement of mammalian target of rapamycin (mTOR) activity, 
      dysregulation of cell growth, and tumorigenesis. Signaling via mTOR plays a role 
      in multifaceted genomic responses, but its effectors in the brain are largely 
      unknown. Therefore, gene expression profiling on four SEGAs was performed with 
      Affymetrix Human Genome arrays. Of the genes differentially expressed in TSC, 11 
      were validated by real-time PCR on independent tumor samples and 3 SEGA-derived 
      cultures. Expression of several proteins was confirmed by immunohistochemistry. 
      The differentially-regulated proteins were mainly involved in tumorigenesis and 
      nervous system development. ANXA1, GPNMB, LTF, RND3, S100A11, SFRP4, and NPTX1 
      genes were likely to be mTOR effector genes in SEGA, as their expression was 
      modulated by an mTOR inhibitor, rapamycin, in SEGA-derived cells. Inhibition of 
      mTOR signaling affected size of cultured SEGA cells but had no influence on their 
      proliferation, morphology, or migration, whereas inhibition of both mTOR and 
      extracellular signal-regulated kinase signaling pathways led to significant 
      alterations of these processes. For the first time, we identified genes related 
      to the occurrence of SEGA and regulated by mTOR and demonstrated an effective 
      modulation of SEGA growth by pharmacological inhibition of both mTOR and 
      extracellular signal-regulated kinase signaling pathways, which could represent a 
      novel therapeutic approach.
FAU - Tyburczy, Magdalena Ewa
AU  - Tyburczy ME
AD  - The Nencki Institute of Experimental Biology, Warsaw, Poland.
FAU - Kotulska, Katarzyna
AU  - Kotulska K
FAU - Pokarowski, Piotr
AU  - Pokarowski P
FAU - Mieczkowski, Jakub
AU  - Mieczkowski J
FAU - Kucharska, Joanna
AU  - Kucharska J
FAU - Grajkowska, Wieslawa
AU  - Grajkowska W
FAU - Roszkowski, Maciej
AU  - Roszkowski M
FAU - Jozwiak, Sergiusz
AU  - Jozwiak S
FAU - Kaminska, Bozena
AU  - Kaminska B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100204
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Astrocytes/cytology
MH  - Astrocytoma/*metabolism
MH  - Bromodeoxyuridine/pharmacology
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Giant Cells/*cytology
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - Models, Biological
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tuberous Sclerosis/*metabolism
PMC - PMC2843477
EDAT- 2010/02/06 06:00
MHDA- 2010/12/16 06:00
PMCR- 2011/04/01
CRDT- 2010/02/06 06:00
PHST- 2010/02/06 06:00 [entrez]
PHST- 2010/02/06 06:00 [pubmed]
PHST- 2010/12/16 06:00 [medline]
PHST- 2011/04/01 00:00 [pmc-release]
AID - S0002-9440(10)60500-7 [pii]
AID - 10.2353/ajpath.2010.090950 [doi]
PST - ppublish
SO  - Am J Pathol. 2010 Apr;176(4):1878-90. doi: 10.2353/ajpath.2010.090950. Epub 2010 
      Feb 4.