Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Eißmann, M; Melzer, IM; Fernández, SB; Michel, G; Hrabě de Angelis, M; Hoefler, G; Finkenwirth, P; Jauch, A; Schoell, B; Grez, M; Schmidt, M; Bartholomae, CC; Newrzela, S; Haetscher, N; Rieger, MA; Zachskorn, C; Mittelbronn, M; Zörnig, M.
Overexpression of the anti-apoptotic protein AVEN contributes to increased malignancy in hematopoietic neoplasms.
Oncogene. 2013; 32(20):2586-2591
Doi: 10.1038/onc.2012.263
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- Co-authors Med Uni Graz
- Höfler Gerald
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adaptor Proteins, Signal Transducing - genetics
- Animals -
- Apoptosis Regulatory Proteins - genetics
- Base Sequence -
- Cell Line, Tumor -
- Gene Expression Regulation, Leukemic -
- Gene Knockdown Techniques -
- Genes, p53 -
- Humans -
- Lymphoma, T-Cell - genetics
- Membrane Proteins - genetics
- Mice -
- Mice, Inbred C57BL -
- Mice, Transgenic -
- Molecular Sequence Data -
- Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics
- Thymocytes - physiology
- Xenograft Model Antitumor Assays -
- Find related publications in this database (Keywords)
- AVEN
- apoptosis
- T-ALL
- acute lymphoblastic leukemia
- p53
- transgenic mice