PMID- 22751129
OWN - NLM
STAT- MEDLINE
DCOM- 20130715
LR  - 20130516
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 32
IP  - 20
DP  - 2013 May 16
TI  - Overexpression of the anti-apoptotic protein AVEN contributes to increased 
      malignancy in hematopoietic neoplasms.
PG  - 2586-91
LID - 10.1038/onc.2012.263 [doi]
AB  - AVEN has been identified as an inhibitor of apoptosis, which binds to the adaptor 
      protein, APAF-1, and thereby prevents apoptosome formation and mitochondrial 
      apoptosis. Recent data have demonstrated high expression levels of AVEN messenger 
      RNA in acute leukemias as well as a positive correlation between AVEN mRNA 
      overexpression and poor prognosis in childhood acute lymphoblastic leukemia. On 
      the basis of these data, we investigated the potential involvement of AVEN in 
      tumorigenesis. First, we confirmed the overexpression of AVEN in T-cell acute 
      lymphoblastic leukemia/lymphoma (T-ALL) patient samples. We then established a 
      transgenic mouse model with T-cell-specific overexpression of AVEN, with which we 
      demonstrated the oncogenic cooperation of AVEN with heterozygous loss of p53. 
      Finally, we used a subcutaneous xenograft mouse model to show that AVEN knockdown 
      in the T-ALL cell lines, MOLT-4 and CCRF-CEM, and in the acute myeloblastic 
      leukemia cell line, Kasumi-1, leads to a halt in tumor growth owing to the 
      increased apoptosis and decreased proliferation of tumor cells. Collectively, our 
      data demonstrate that the anti-apoptotic molecule, AVEN, functions as an 
      oncoprotein in hematopoietic neoplasms.
FAU - Eissmann, M
AU  - Eissmann M
AD  - Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus, Frankfurt, Germany.
FAU - Melzer, I M
AU  - Melzer IM
FAU - Fernandez, S B M
AU  - Fernandez SB
FAU - Michel, G
AU  - Michel G
FAU - Hrabe de Angelis, M
AU  - Hrabe de Angelis M
FAU - Hoefler, G
AU  - Hoefler G
FAU - Finkenwirth, P
AU  - Finkenwirth P
FAU - Jauch, A
AU  - Jauch A
FAU - Schoell, B
AU  - Schoell B
FAU - Grez, M
AU  - Grez M
FAU - Schmidt, M
AU  - Schmidt M
FAU - Bartholomae, C C
AU  - Bartholomae CC
FAU - Newrzela, S
AU  - Newrzela S
FAU - Haetscher, N
AU  - Haetscher N
FAU - Rieger, M A
AU  - Rieger MA
FAU - Zachskorn, C
AU  - Zachskorn C
FAU - Mittelbronn, M
AU  - Mittelbronn M
FAU - Zornig, M
AU  - Zornig M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120702
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (AVEN protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics/metabolism
MH  - Animals
MH  - Apoptosis Regulatory Proteins/*genetics/metabolism
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Leukemic
MH  - Gene Knockdown Techniques
MH  - Genes, p53
MH  - Humans
MH  - Lymphoma, T-Cell/genetics
MH  - Membrane Proteins/*genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics
MH  - Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology
MH  - Thymocytes/physiology
MH  - Xenograft Model Antitumor Assays
EDAT- 2012/07/04 06:00
MHDA- 2013/07/17 06:00
CRDT- 2012/07/04 06:00
PHST- 2012/07/04 06:00 [entrez]
PHST- 2012/07/04 06:00 [pubmed]
PHST- 2013/07/17 06:00 [medline]
AID - onc2012263 [pii]
AID - 10.1038/onc.2012.263 [doi]
PST - ppublish
SO  - Oncogene. 2013 May 16;32(20):2586-91. doi: 10.1038/onc.2012.263. Epub 2012 Jul 2.