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

Front Biosci (Landmark Ed). 2009 Jan 1;14:2944-58. doi: 10.2741/3425.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human