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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
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Protein kinase C delta is activated in mouse ovarian surface epithelial cancer cells by

Shalmica R Williams1, Deok-Soo Son, Paul F Terranova

  • 1Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.

Toxicology
|December 31, 2003
PubMed

Insights

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activates protein kinase C delta (PKCdelta) in ovarian cancer cells. This study reveals TCDD

Area of Science:

  • Cell biology
  • Molecular toxicology
  • Cancer research

Background:

  • The interactions between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and protein kinase C (PKC) signaling pathways are cell- and tissue-specific.
  • The physiological significance of these interactions remains unclear, particularly in the context of ovarian cancer.

Purpose of the Study:

  • To investigate the effects of TCDD on the PKC signaling pathway in a mouse ovarian surface epithelial cancer cell line (ID8).
  • To determine the specific PKC isoforms involved in TCDD's mechanism of action.

Main Methods:

  • Treatment of ID8 cells with TCDD and phorbol-12-myristate-13-acetate (PMA).
  • Inhibition of PKC using BisI and Rotterlin.
  • Western blot analysis to assess protein expression.
  • Immunofluorescent microscopy for subcellular localization studies.
  • Kinase activity assays to measure total PKC and PKCdelta activity.

Main Results:

  • Phorbol-12-myristate-13-acetate (PMA) potentiated TCDD-induced EROD activity, an effect abolished by PKC inhibitors, indicating PKC enhances TCDD signaling.
  • TCDD significantly increased PKCdelta protein expression in a dose-dependent manner and promoted its translocation to the perinuclear area and nuclear structures.
  • TCDD induced biphasic increases in both total PKC and PKCdelta-specific kinase activities.

Conclusions:

  • TCDD preferentially induces PKCdelta protein expression, phosphotransferase activity, and membrane translocation in ID8 ovarian cancer cells.
  • PKCdelta may function as an intracellular effector molecule for TCDD-mediated biological events in this ovarian cancer model.

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