PMID- 16912221
OWN - NLM
STAT- MEDLINE
DCOM- 20070117
LR  - 20211203
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 108
IP  - 13
DP  - 2006 Dec 15
TI  - Syk-dependent mTOR activation in follicular lymphoma cells.
PG  - 4156-62
AB  - The mammalian target of rapamycin (mTOR) is emerging as a promising target for 
      antitumor therapy. However, the mechanism that contributes to its regulation in B 
      lymphomas remains unknown. This study shows that in follicular lymphoma (FL) 
      cells, mTOR is active because the cells displayed rapamycin-sensitive 
      phosphorylation of p70S6 kinase and 4E-BP1. Moreover, immunohistochemistry 
      applied on lymph node tissue sections obtained from patients with FL revealed 
      that, in most cases, p70S6 kinase was highly phosphorylated compared to normal 
      tonsillar tissue. In FL cells, mTOR was under control of both phospholipase D 
      (PLD) and phosphatidylinositol 3-kinase (PI3K). Moreover, we demonstrated that 
      Syk plays a central role in mTOR activation because we found that both expression 
      and activity are elevated compared to normal or chronic lymphocytic leukemia B 
      cells. We also provide evidence that Syk operates through PLD- and 
      PI3K-independent pathways. Finally, Syk inhibition by piceatannol or by siRNA 
      plasmids resulted in a potent inhibition of mTOR activity in FL cells, as well as 
      in mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma. 
      These findings suggest that the Syk-mTOR pathway has a critical function in FL 
      survival, and therefore, that Syk could be a promising new target for B-lymphoma 
      therapy.
FAU - Leseux, Ludivine
AU  - Leseux L
AD  - INSERM U563-Centre de Physiopathologie Toulouse Purpan (CPTP), Departement 
      d'Oncogenese et Signalisation dans les Cellules Hematopoietiques, Centre 
      Hospitalier Universitaire (CHU) Purpan-BP3028, Toulouse, France.
FAU - Hamdi, Safouane M
AU  - Hamdi SM
FAU - Al Saati, Talal
AU  - Al Saati T
FAU - Capilla, Florence
AU  - Capilla F
FAU - Recher, Christian
AU  - Recher C
FAU - Laurent, Guy
AU  - Laurent G
FAU - Bezombes, Christine
AU  - Bezombes C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060815
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Stilbenes)
RN  - 6KS3LS0D4F (3,3',4,5'-tetrahydroxystilbene)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.4.4 (Phospholipase D)
SB  - IM
MH  - Burkitt Lymphoma/drug therapy/enzymology/pathology
MH  - Cell Line, Tumor
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/enzymology/pathology
MH  - Lymph Nodes/metabolism/pathology
MH  - Lymphoma, B-Cell/drug therapy/enzymology/pathology
MH  - Lymphoma, Follicular/drug therapy/*enzymology/pathology
MH  - Lymphoma, Mantle-Cell/drug therapy/enzymology/pathology
MH  - Neoplasm Proteins/*metabolism
MH  - Palatine Tonsil/enzymology/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phospholipase D/metabolism
MH  - Protein Kinases/*metabolism
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - RNA, Small Interfering/genetics/pharmacology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - *Signal Transduction/drug effects
MH  - Stilbenes/pharmacology
MH  - Syk Kinase
MH  - TOR Serine-Threonine Kinases
EDAT- 2006/08/17 09:00
MHDA- 2007/01/18 09:00
CRDT- 2006/08/17 09:00
PHST- 2006/08/17 09:00 [pubmed]
PHST- 2007/01/18 09:00 [medline]
PHST- 2006/08/17 09:00 [entrez]
AID - S0006-4971(20)52213-1 [pii]
AID - 10.1182/blood-2006-05-026203 [doi]
PST - ppublish
SO  - Blood. 2006 Dec 15;108(13):4156-62. doi: 10.1182/blood-2006-05-026203. Epub 2006 
      Aug 15.