PKCalpha expression is a marker for breast cancer aggressiveness.
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.
Lønne
Gry Kalstad
GK
Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, SE- 205 02 Malmö, Sweden. Gry.Kalstad_Lonne@med.lu.se
Cornmark
Louise
L
Zahirovic
Iris Omanovic
IO
Landberg
Göran
G
Jirström
Karin
K
Larsson
Christer
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D018613:Microscopy, Confocal; D008875:Middle Aged; D011379:Prognosis; D051571:Protein Kinase C-alpha / Q000096:biosynthesis* / Q000235:genetics; D051745:Protein Kinase C-delta / Q000096:biosynthesis / Q000235:genetics; D051744:Protein Kinase C-epsilon / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon
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