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.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Walther Hall, 980 W Walnut Street, C230, Indianapolis, IN 46202, USA. ypolar@iupui.edu
authors.forename: Yesim
authors.initials: Y
authors.lastname: Gökmen-Polar
authors.forename: Rutika
authors.initials: R
authors.lastname: Mehta
authors.forename: Sukru
authors.initials: S
authors.lastname: Tuzmen
authors.forename: Spyro
authors.initials: S
authors.lastname: Mousses
authors.forename: Mangesh A
authors.initials: MA
authors.lastname: Thorat
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Sanders
authors.forename: Dmitry
authors.initials: D
authors.lastname: Turbin
authors.forename: Samuel
authors.initials: S
authors.lastname: Leung
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
authors.forename: Sunil
authors.initials: S
authors.lastname: Badve
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053555:Keratin-5 / Q000378:metabolism; D053553:Keratin-6 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D011379:Prognosis; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013997:Time Factors; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; D053555:Keratin-5; D053553:Keratin-6; D019394:Ki-67 Antigen; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D042461:Vascular Endothelial Growth Factor A; C503940:KRT5 protein, human; C467484:VEGFA protein, human; C496540:PTGS2 protein, human; C508053:ERBB2 protein, human