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PKCalpha expression is a marker for breast cancer aggressiveness
Gry Kalstad Lønne1, Louise Cornmark, Iris Omanovic Zahirovic
1Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, SE- 205 02 Malmö, Sweden. Gry.Kalstad_Lonne@med.lu.se
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.
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