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c-Jun N-terminal kinase regulates apoptosis in endometrial cancer cells

Elaine M Reno1, James M Haughian, Twila A Jackson

  • 1Department of Obstetrics and Gynecology, Section of Basic Reproductive Sciences, School of Medicine, University of Colorado Denver, Mail Stop 8309, 12800 E. 19th Avenue, Aurora, CO 80045, USA.

Apoptosis : an International Journal on Programmed Cell Death
|May 9, 2009
PubMed

Insights

c-Jun N-terminal kinases (JNKs) and protein kinase C delta (PKCdelta) regulate apoptosis in endometrial cancer. Their activity influences sensitivity to chemotherapy, suggesting a tumor suppressor role.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Research

Background:

  • c-Jun N-terminal kinases (JNKs) are key regulators of cell proliferation and apoptosis, implicated in tumorigenesis.
  • Endometrial cancer presents distinct subtypes (Type I and Type II) with varying cellular mechanisms.

Purpose of the Study:

  • To investigate the role of JNKs in apoptotic responses in Type I (Ishikawa) and Type II (HEC-50) endometrial cancer cells.
  • To explore the interplay between JNK, MAP kinase kinase 4 (MKK4), and protein kinase C delta (PKCdelta) in regulating apoptosis and chemoresistance.

Main Methods:

  • Utilized etoposide treatment and UV irradiation to induce JNK activation and apoptosis in endometrial cancer cell lines.
  • Employed JNK and MKK4 inhibition, alongside PKCdelta knockdown, to assess their impact on apoptotic pathways.
  • Differentiated between stimulus-dependent and cell-type-specific signaling pathways.

Main Results:

  • Sustained JNK activation correlated with apoptosis induction following etoposide or UV treatment.
  • Inhibition of JNK or MKK4 selectively suppressed apoptosis in both cell types.
  • PKCdelta knockdown attenuated apoptosis and affected UV-mediated JNK activation in HEC-50 cells, but not Ishikawa cells, indicating stimulus and cell-type-specific roles.

Conclusions:

  • JNK regulates apoptosis via both PKCdelta-dependent and independent pathways, contingent on the stimulus and cell type.
  • JNK and PKCdelta expression and activity in endometrial cancer cells modulate apoptosis and chemosensitivity.
  • These kinases may function as tumor suppressors in endometrial cancer, impacting therapeutic strategies.

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