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

Yesim 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 Citations (Scopus)

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

Fingerprint

Protein Kinase C
Breast Neoplasms
Cell Line
Nuclear Proteins
Messenger RNA
Cyclooxygenase 2
Estrogen Receptors
Vascular Endothelial Growth Factor A
Proteins
Immunohistochemistry
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Differential subcellular expression of protein kinase C betaII in breast cancer : Correlation with breast cancer subtypes. / Polar, Yesim; Mehta, Rutika; Tuzmen, Sukru; Mousses, Spyro; Thorat, Mangesh A.; Sanders, Kerry L.; Turbin, Dmitry; Leung, Samuel; Huntsman, David G.; Sledge, George W.; Badve, Sunil.

In: Breast Cancer Research and Treatment, Vol. 124, No. 2, 11.2010, p. 327-335.

Research output: Contribution to journalArticle

Polar, Y, Mehta, R, Tuzmen, S, Mousses, S, Thorat, MA, Sanders, KL, Turbin, D, Leung, S, Huntsman, DG, Sledge, GW & Badve, S 2010, 'Differential subcellular expression of protein kinase C betaII in breast cancer: Correlation with breast cancer subtypes', Breast Cancer Research and Treatment, vol. 124, no. 2, pp. 327-335. https://doi.org/10.1007/s10549-010-0733-2
Polar, Yesim ; Mehta, Rutika ; Tuzmen, Sukru ; Mousses, Spyro ; Thorat, Mangesh A. ; Sanders, Kerry L. ; Turbin, Dmitry ; Leung, Samuel ; Huntsman, David G. ; Sledge, George W. ; Badve, Sunil. / Differential subcellular expression of protein kinase C betaII in breast cancer : Correlation with breast cancer subtypes. In: Breast Cancer Research and Treatment. 2010 ; Vol. 124, No. 2. pp. 327-335.
@article{1762d9aa5e9645bd88a65874115f115b,
title = "Differential subcellular expression of protein kinase C betaII in breast cancer: Correlation with breast cancer subtypes",
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.",
keywords = "Breast cancer, Human epidermal growth factor receptor-2, Protein kinase C betaII, Subcellular localization, Tissue microarray",
author = "Yesim Polar and Rutika Mehta and Sukru Tuzmen and Spyro Mousses and Thorat, {Mangesh A.} and Sanders, {Kerry L.} and Dmitry Turbin and Samuel Leung and Huntsman, {David G.} and Sledge, {George W.} and Sunil Badve",
year = "2010",
month = "11",
doi = "10.1007/s10549-010-0733-2",
language = "English",
volume = "124",
pages = "327--335",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Differential subcellular expression of protein kinase C betaII in breast cancer

T2 - Correlation with breast cancer subtypes

AU - Polar, Yesim

AU - Mehta, Rutika

AU - Tuzmen, Sukru

AU - Mousses, Spyro

AU - Thorat, Mangesh A.

AU - Sanders, Kerry L.

AU - Turbin, Dmitry

AU - Leung, Samuel

AU - Huntsman, David G.

AU - Sledge, George W.

AU - Badve, Sunil

PY - 2010/11

Y1 - 2010/11

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Human epidermal growth factor receptor-2

KW - Protein kinase C betaII

KW - Subcellular localization

KW - Tissue microarray

UR - http://www.scopus.com/inward/record.url?scp=78649331684&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649331684&partnerID=8YFLogxK

U2 - 10.1007/s10549-010-0733-2

DO - 10.1007/s10549-010-0733-2

M3 - Article

C2 - 20099025

AN - SCOPUS:78649331684

VL - 124

SP - 327

EP - 335

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 2

ER -