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Protein kinase C delta enhances proliferation and survival of murine mammary cells

Valeria C Grossoni1, Karina B Falbo, Marcelo G Kazanietz

  • 1Research Area, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Buenos Aires, Argentina.

Molecular Carcinogenesis
|January 16, 2007
PubMed

Insights

Protein kinase C delta (PKCdelta) surprisingly promotes mammary cell proliferation and survival, contradicting its proposed tumor suppressor role. Further research is needed to understand its context-dependent functions in cancer therapy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Protein kinase C delta (PKCdelta) is a serine-threonine kinase implicated in cell proliferation and apoptosis.
  • Previous studies suggested PKCdelta acts as a tumor suppressor, inhibiting cell growth.

Purpose of the Study:

  • To investigate the role of PKCdelta in mammary cell proliferation and survival.
  • To determine the signaling pathways modulated by PKCdelta in immortalized mammary cells.

Main Methods:

  • Overexpression of PKCdelta in murine NMuMG mammary cells.
  • Assessing [3H]-thymidine incorporation and cell proliferation.
  • Analyzing extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) activation.
  • Evaluating cyclin D1 expression, Rb phosphorylation, and Akt pathway activation.
  • Testing resistance to apoptotic stimuli (serum deprivation, doxorubicin).

Main Results:

  • PKCdelta overexpression significantly increased cell proliferation and [3H]-thymidine incorporation.
  • PKCdelta enhanced ERK-MAPK activation, cyclin D1 expression, and Rb hyperphosphorylation.
  • Ectopic PKCdelta expression promoted anchorage-independent growth.
  • PKCdelta overexpressors exhibited increased resistance to apoptosis via Akt pathway hyperactivation.

Conclusions:

  • PKCdelta acts as a positive modulator of proliferation and survival signals in immortalized mammary cells.
  • PKCdelta's function is context-dependent, necessitating careful study in different cell types.
  • Caution is advised when considering PKCdelta as a cancer therapy target due to its complex roles.

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