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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2009

Authors: Ecker, A; Simma, O; Hoelbl, A; Kenner, L; Beug, H; Moriggl, R; Sexl, V

Title: The dark and the bright side of Stat3: proto-oncogene and tumor-suppressor.

Source: Front Biosci (Landmark Ed). 2009; 14:2944-2958



Authors Vetmeduni Vienna:

Hölbl-Kovacic Andrea
Kenner Lukas
Sexl Veronika


Project(s): CDK6 - ein therapeutischer Angriffspunkt in Leukämien?


Abstract:
Stat transcription factors have been implicated in tumorigenesis in mice and men. Stat3 and Stat5 are considered powerful proto-oncogenes, whereas Stat1 has been demonstrated to suppress tumor formation. We demonstrate here for the first time that a constitutive active version of Stat3alpha (Stat3alphaC) may also suppress transformation. Mouse embryonic fibroblasts (MEFs) deficient for p53 can be transformed with either c-myc or with rasV12 alone. Interestingly, transformation by c-myc is efficiently suppressed by co-expression of Stat3alphaC, but Stat3alphaC does not interfere with transformation by the rasV12-oncogene. In contrast, transplantation of bone marrow cells expressing Stat3alphaC induces the formation of a highly aggressive T cell leukemia in mice. The leukemic cells invaded multiple organs including lung, heart, salivary glands, liver and kidney. Interestingly, transplanted mice developed a similar leukemia when the bone marrow cells were transduced with Stat3beta, which is also constitutively active when expressed at significant levels. Our experiments demonstrate that Stat3 has both - tumor suppressing and tumor promoting properties.

Keywords Pubmed: Animals
Blotting, Western
Bone Marrow Transplantation
Cell Line
Cell Proliferation
Electrophoretic Mobility Shift Assay
Flow Cytometry
Genes, Tumor Suppressor*
Humans
Leukemia/physiopathology
Male
Mice
Mice, Inbred C57BL
Proto-Oncogenes*
Reverse Transcriptase Polymerase Chain Reaction
STAT3 Transcription Factor/genetics
STAT3 Transcription Factor/physiology*


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