Constitutive activation of stat 3 oncogene product in human ovarian carcinoma cells

Gynecol Oncol. 2000 Oct;79(1):67-73. doi: 10.1006/gyno.2000.5931.


Objective: Stat 3 functions in transducing signals from the cell's surface to its nucleus and activation of gene transcription. Aberrations of Stat 3 in breast cancer have raised the possibility of its contribution to oncogenesis. Our goal was to examine ovarian cancer cell lines to determine whether Stat 3 plays a relevant role in ovarian carcinogenesis.

Methods: Protein lysates were extracted from normal ovarian surface epithelial cells and malignant cells. Western blotting techniques were performed with phosphorylation-independent or phosphorylation-specific Stat 3 (tyrosine 705) antibody. Confirmation of Stat 3 activation was determined by a luciferase reporter driven by a promoter containing Stat 3-specific binding sites. Bcl-x(L) and cyclin D(1) were also analyzed by Western blotting.

Results: MDAH 2774, OV-1063, Caov-3, and O.C. 22819 expressed high levels of phosphorylated Stat 3. In contrast, A2780 and normal ovarian surface epithelial cells had little Stat 3 phosphorylation recognized. Confirmation of persistent activation of Stat 3 activity was shown by transfection of cells with a Stat 3 luciferase reporter. Potential downstream mediators of Stat 3 including Bcl-x(L) and cyclin D(1) were also evaluated. In cells expressing activated Stat 3, high levels of both Bcl-x(L) and cyclin D(1) were detected, whereas in A2780 cells, which did not express activated Stat 3, only low levels of Bcl-x(L) and cyclin D(1) were expressed.

Conclusions: Constitutive activation of Stat 3 is present in ovarian cancer lines but not in normal ovarian surface epithelial cells. Activation of Stat 3 is a common event during oncogenic transformation upstream to both Bcl-x(L) and cyclin D(1). The relationship of this aberrancy of ovarian carcinoma harboring activated Stat 3 deserves further investigation.

MeSH terms

  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoblotting
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Phosphorylation
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • STAT3 Transcription Factor
  • Signal Transduction / physiology
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • bcl-X Protein


  • BCL2L1 protein, human
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • bcl-X Protein
  • Cyclin D1