PMID- 20015877
OWN - NLM
STAT- MEDLINE
DCOM- 20111005
LR  - 20211020
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 95
IP  - 5
DP  - 2010 May
TI  - C/EBPbeta expression in ALK-positive anaplastic large cell lymphomas is required for 
      cell proliferation and is induced by the STAT3 signaling pathway.
PG  - 760-7
LID - 10.3324/haematol.2009.014050 [doi]
AB  - BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell 
      lymphoma is characterized by the t(2;5) chromosomal translocation, resulting in 
      the expression of a fusion protein formed of nucleophosmin (NPM) and ALK. 
      Recently, we reported the abnormal expression of the transcription factor 
      CCAAT/enhancer binding protein-beta (C/EBPbeta) in ALK-positive anaplastic large 
      cell lymphomas, and demonstrated its dependence on NPM-ALK activity. DESIGN AND 
      METHODS: In this study, the role of C/EBPbeta in proliferation and survival of 
      ALK-positive anaplastic large cell lymphomas was investigated, as well as the 
      mechanism of its expression and activity. Highly effective short hairpin RNA 
      sequences and/or pharmacological inhibitors were used to abrogate the expression 
      or activity of C/EBPbeta, signal transducer and activator of transcription 3 
      (STAT3), AKT, extracellular signal-related kinase 1/2 (ERK1/2) and mammalian 
      target of rapamycin (mTOR). RESULTS: Interference with C/EBPbeta expression 
      resulted in a dramatic decrease in cell proliferation in ALK-positive anaplastic 
      large cell lymphomas, with a mild induction of apoptosis after 6 days. 
      Down-regulation of STAT3 resulted in a marked decrease in C/EBPbeta mRNA and 
      protein levels with impairment in cell proliferation and viability, underscoring 
      the important role of these two proteins in ALK-mediated oncogenesis. 
      Additionally, we demonstrated that reduction of ERK1/2 activity led to C/EBPbeta 
      Thr(235) dephosphorylation and moderate growth retardation. The AKT/mTOR 
      signaling pathway did not have any influence on C/EBPbeta expression or C/EBPbeta 
      phosphorylation. CONCLUSIONS: These findings reveal the convergence of STAT3 and 
      ERK1/2 signaling pathways activated by NPM-ALK in mediating the regulation of 
      C/EBPbeta expression, a transcription factor central to NPM-ALK transformation.
FAU - Anastasov, Natasa
AU  - Anastasov N
AD  - Institute of Pathology, Helmholtz Center Munich, German Research Center for 
      Environmental Health, Germany.
FAU - Bonzheim, Irina
AU  - Bonzheim I
FAU - Rudelius, Martina
AU  - Rudelius M
FAU - Klier, Margit
AU  - Klier M
FAU - Dau, Therese
AU  - Dau T
FAU - Angermeier, Daniela
AU  - Angermeier D
FAU - Duyster, Justus
AU  - Duyster J
FAU - Pittaluga, Stefania
AU  - Pittaluga S
FAU - Fend, Falko
AU  - Fend F
FAU - Raffeld, Mark
AU  - Raffeld M
FAU - Quintanilla-Martinez, Leticia
AU  - Quintanilla-Martinez L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091216
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Alk protein, mouse)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Anaplastic Lymphoma Kinase
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-beta/antagonists & inhibitors/*biosynthesis
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Cell Line, Tumor
MH  - *Cell Proliferation
MH  - Cell Survival/genetics
MH  - Down-Regulation/genetics
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lymphoma, Large-Cell, Anaplastic/*enzymology/pathology
MH  - Mice
MH  - Receptor Protein-Tyrosine Kinases/*biosynthesis
MH  - STAT3 Transcription Factor/antagonists & inhibitors/*physiology
MH  - *Signal Transduction/genetics
PMC - PMC2864382
EDAT- 2009/12/18 06:00
MHDA- 2011/10/06 06:00
PMCR- 2010/05/01
CRDT- 2009/12/18 06:00
PHST- 2009/12/18 06:00 [entrez]
PHST- 2009/12/18 06:00 [pubmed]
PHST- 2011/10/06 06:00 [medline]
PHST- 2010/05/01 00:00 [pmc-release]
AID - haematol.2009.014050 [pii]
AID - 0950760 [pii]
AID - 10.3324/haematol.2009.014050 [doi]
PST - ppublish
SO  - Haematologica. 2010 May;95(5):760-7. doi: 10.3324/haematol.2009.014050. Epub 2009 
      Dec 16.