PKCalpha expression is a marker for breast cancer aggressiveness

Mol Cancer. 2010 Apr 14:9:76. doi: 10.1186/1476-4598-9-76.

Abstract

Background: Protein kinase C (PKC) isoforms are potential targets for breast cancer therapy. This study was designed to evaluate which PKC isoforms might be optimal targets for different breast cancer subtypes.

Results: In two cohorts of primary breast cancers, PKCalpha levels correlated to estrogen and progesterone receptor negativity, tumor grade, and proliferative activity, whereas PKCdelta and PKCepsilon did not correlate to clinicopathological parameters. Patients with PKCalpha-positive tumors showed poorer survival than patients with PKCalpha-negative tumors independently of other factors. Cell line studies demonstrated that PKCalpha levels are high in MDA-MB-231 and absent in T47D cells which proliferated slower than other cell lines. Furthermore, PKCalpha silencing reduced proliferation of MDA-MB-231 cells. PKCalpha inhibition or downregulation also reduced cell migration in vitro.

Conclusions: PKCalpha is a marker for poor prognosis of breast cancer and correlates to and is important for cell functions associated with breast cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Microscopy, Confocal
  • Middle Aged
  • Prognosis
  • Protein Kinase C-alpha / biosynthesis*
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-delta / biosynthesis
  • Protein Kinase C-delta / genetics
  • Protein Kinase C-epsilon / biosynthesis
  • Protein Kinase C-epsilon / genetics
  • RNA, Small Interfering
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / biosynthesis
  • Receptors, Progesterone / genetics
  • Transfection

Substances

  • Biomarkers, Tumor
  • RNA, Small Interfering
  • Receptors, Estrogen
  • Receptors, Progesterone
  • PRKCA protein, human
  • Protein Kinase C-alpha
  • Protein Kinase C-delta
  • Protein Kinase C-epsilon