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GPI-anchor structure
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Related Experiment Video

Updated: Feb 9, 2026

GPI Anchoring of Proteins in the ER Membrane
01:29

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Stat3 as an oncogene.

J F Bromberg1, M H Wrzeszczynska, G Devgan

  • 1Laboratory of Molecular Cell Biology, The Rockefeller University, New York, New York 10021-6399, USA.

Cell
|August 24, 1999
PubMed
Summary
This summary is machine-generated.

Constitutive activation of Signal Transducer and Activator of Transcription 3 (Stat3) can drive cancer. A modified Stat3 molecule (Stat3-C) spontaneously dimerizes, activates transcription, and causes cellular transformation.

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Related Experiment Videos

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Area of Science:

  • Molecular Biology
  • Oncology
  • Signal Transduction

Background:

  • Signal Transducers and Activators of Transcription (STATs) are key transcription factors mediating cellular responses to cytokines and growth factors.
  • Persistent activation of Stat3 is observed in numerous human cancers and transformed cell lines, where it plays roles in transformation and apoptosis resistance.

Purpose of the Study:

  • To investigate the oncogenic potential of a constitutively active Stat3 molecule.
  • To determine if Stat3 activation alone is sufficient for cellular transformation.

Main Methods:

  • Site-directed mutagenesis was used to substitute two cysteine residues in the SH2 domain of Stat3, creating a constitutively active Stat3-C molecule.
  • The functional properties of Stat3-C, including dimerization, DNA binding, and transcriptional activity, were assessed.
  • Cellular transformation was evaluated by soft agar colony formation assays and tumor formation in nude mice.

Main Results:

  • The engineered Stat3-C molecule exhibited spontaneous dimerization, DNA binding, and transcriptional activation.
  • Expression of Stat3-C in immortalized fibroblasts induced cellular transformation, evidenced by anchorage-independent growth (soft agar colonies) and tumor formation in vivo.
  • These findings demonstrate that activated Stat3 can mediate cellular transformation independently.

Conclusions:

  • Constitutive activation of Stat3 is a significant mechanism driving cellular transformation and tumorigenesis.
  • The study highlights the critical role of persistent Stat3 activation in the development and progression of human tumors.