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Protein kinase G type Ialpha activity in human ovarian cancer cells significantly contributes to enhanced Src

Elaine L Leung1, Janica C Wong, Mary G Johlfs

  • 1Nevada Cancer Institute, Las Vegas, Nevada.

Molecular Cancer Research : MCR
|April 8, 2010
PubMed

Insights

Basal nitric oxide (NO)/cyclic GMP (cGMP)/protein kinase G (PKG) signaling promotes ovarian cancer cell proliferation by regulating Src family kinase (SFK) activity. Targeting this pathway offers a potential therapeutic strategy for ovarian cancer.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Signaling

Background:

  • The nitric oxide (NO)/cyclic GMP (cGMP)/protein kinase G (PKG) pathway is known to protect against apoptosis in ovarian cancer cells.
  • The predominant PKG isoform in ovarian cancer cells is PKG-Ialpha.

Purpose of the Study:

  • To investigate the role of basal PKG kinase activity in regulating Src family kinase (SFK) activity and proliferation in human ovarian cancer cells.
  • To elucidate the interaction between SFK and PKG-Ialpha in ovarian cancer cell proliferation.

Main Methods:

  • Utilized inhibitors of NO/cGMP biosynthesis (ODQ) and PKG-Ialpha kinase activity (DT-2).
  • Employed PKG-Ialpha knockdown via small interfering RNA (siRNA) and SFK inhibitor (SKI-1).
  • Assessed DNA synthesis using bromodeoxyuridine incorporation and measured protein phosphorylation status.

Main Results:

  • Basal cGMP/PKG-Ialpha kinase activity and SFK activity are crucial for ovarian cancer cell proliferation.
  • SFK activity is dependent on PKG-Ialpha kinase activity, and SFK contributes to PKG-Ialpha tyrosine phosphorylation.
  • Direct interaction between c-Src and PKG-Ialpha enhances Src kinase activity and PKG-Ialpha phosphorylation.

Conclusions:

  • The interaction between Src and PKG-Ialpha plays a significant role in promoting DNA synthesis and proliferation in human ovarian cancer cells.
  • The NO/cGMP/PKG-Ialpha signaling pathway represents a potential therapeutic target for inhibiting ovarian cancer cell proliferation.

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