The dark and the bright side of Stat3: proto-oncogene and tumor-suppressor.
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.
Ecker
Andrea
A
Institute of Molecular Pathology (IMP), Austria.
Simma
Olivia
O
Hoelbl
Andrea
A
Kenner
Lukas
L
Beug
Hartmut
H
Moriggl
Richard
R
Sexl
Veronika
V
D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D002460:Cell Line; D049109:Cell Proliferation; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor; D006801:Humans; D007938:Leukemia / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000502:physiology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human