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. Sledge, Sunil Badve

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)327-335
Number of pages9
JournalBreast Cancer Research and Treatment
Volume124
Issue number2
DOIs
StatePublished - Nov 1 2010

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Gökmen-Polar, Y., Mehta, R., Tuzmen, S., Mousses, S., Thorat, M. A., Sanders, K. L., Turbin, D., Leung, S., Huntsman, D. G., Sledge, G. W., & Badve, S. (2010). Differential subcellular expression of protein kinase C betaII in breast cancer: Correlation with breast cancer subtypes. Breast Cancer Research and Treatment, 124(2), 327-335. https://doi.org/10.1007/s10549-010-0733-2