Breast Cancer Research and Treatment

, Volume 124, Issue 2, pp 327–335 | Cite as

Differential subcellular expression of protein kinase C betaII in breast cancer: correlation with breast cancer subtypes

  • Yesim Gökmen-Polar
  • Rutika Mehta
  • Sukru Tuzmen
  • Spyro Mousses
  • Mangesh A. Thorat
  • Kerry L. Sanders
  • Dmitry Turbin
  • Samuel Leung
  • David G. Huntsman
  • George W. SledgeJr.
  • Sunil Badve
Preclinical study


Protein kinase C betaII (PKCβII) represents a novel potential target for anticancer therapies in breast cancer. In order to identify patient subgroups which might benefit from PKC-targeting therapies, we investigated the expression of PKCβII in human breast cancer cell lines and in a tissue microarray (TMA). We first screened breast cancer cell line representatives of breast cancer subtypes for PKCβII expression at the mRNA and at the protein levels. We analyzed a TMA comprising of tumors from 438 patients with a median followup of 15.4 years for PKCβII expression by immunohistochemistry along with other prognostic factors in breast cancer. Among a panel of human breast cancer cell lines, only MDA-MB-436, a triple negative basal cell line, showed overexpression for PKCβII both at the mRNA and at the protein levels. In breast cancer patients, cytoplasmic expression of PKCβII correlated positively with human epidermal growth factor receptor-2 (HER-2; P = 0.01) and Ki-67 (P = 0.016), while nuclear PKCβII correlated positively with estrogen receptor (ER; P = 0.016). The positive correlation of CK5/6 with cytoplasmic PKCβII (P = 0.033) lost statistical significance after adjusting for multiple comparisons (P = 0.198). Cytoplasmic PKCβII did not correlate with cyclooxygenase (COX-2; P = 0.925) and vascular endothelial growth factor (P = 1). There was no significant association between PKCβII staining and overall survival. Cytoplasmic PKCβII correlates with HER-2 and Ki-67, while nuclear PKCβII correlates with ER in breast cancer. Our study suggests the necessity for assessing the subcellular localization of PKCβII in breast cancer subtypes when evaluating the possible effectiveness of PKCβII-targeting agents.


Protein kinase C betaII Breast cancer Human epidermal growth factor receptor-2 Tissue microarray Subcellular localization 



We thank Dr. T.O. Nielsen (University of British Columbia) for providing access to qPCR-based subtyping data. We thank Dr. F.G. Kern (University of Alabama at Birmingham) for the ML20 and MV165 cell lines; Dr. D. J. Slamon for MCF-7/control and MCF-7/HER-2 cell lines (University of California, Los Angeles); Dr. B Shea-Herbert for ME16C cell line (Indiana University School of Medicine); Jamie B. Hadley for the assistance with the confocal microscopy (Indiana University School of Medicine). We also thank Indiana Center for Biological Microscopy for using their facility at the Indiana University. This work was supported by Eli Lilly and Company grant to G.W. Sledge, Jr.

Supplementary material

10549_2010_733_MOESM1_ESM.pdf (137 kb)
Supplementary material 1 (PDF 138 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Yesim Gökmen-Polar
    • 1
  • Rutika Mehta
    • 2
  • Sukru Tuzmen
    • 3
  • Spyro Mousses
    • 3
  • Mangesh A. Thorat
    • 2
  • Kerry L. Sanders
    • 1
  • Dmitry Turbin
    • 4
  • Samuel Leung
    • 4
  • David G. Huntsman
    • 4
  • George W. SledgeJr.
    • 1
    • 2
  • Sunil Badve
    • 1
    • 2
  1. 1.Department of MedicineIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Pathology and Laboratory MedicineIndiana University School of MedicineIndianapolisUSA
  3. 3.Molecular Genetics Laboratory, Pharmaceutical Genomics DivisionTranslational Genomics Research InstituteScottsdaleUSA
  4. 4.Genetic Pathology Evaluation CentreUniversity of British ColumbiaVancouverCanada

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