PKCαand ERβAre Associated with Triple-Negative Breast Cancers in African American and Caucasian Patients

Abstract

Although the incidence of breast cancer in the United States is higher in Caucasian women compared with African American women, African-American patients have more aggressive disease as characterized by a higher percentage of triple-negative breast cancers (TNBCs), high-grade tumors, and a higher mortality rate. PKCα is a biomarker associated with endocrine resistance and poor prognosis and ERβ is emerging as a protective biomarker. Immunohistochemical analysis of ERβ and PKCα expression was performed on 198 formalin-fixed paraffin-embedded primary infiltrating ductal carcinomas from 105 African-American and 93 Caucasian patients. PKCα is positively correlated with TNBC in patients of both races and with high tumor grade in African-American patients. Patients with TNBC express less nuclear ERβ compared with all other subtypes. We find no difference in frequency or intensity of PKCα or ERβ expression between African-American and Caucasian patients. PKCα and ERβ are discussed as potential therapeutic targets for the treatment of patients with TNBC.

RETRACTED ARTICLE: Extranuclear ERα is associated with regression of T47D PKCα-overexpressing, tamoxifen-resistant breast cancer

“…Although the literature is conflicting regarding the level of PKCα expression in breast cancers compared to the normal breast [32-36], variability in PKCα expression amongst breast cancers and the link to endocrine resistance and tumor aggressiveness is clear. Based on three reports in the literature, the prevalence of PKCα expression in all breast cancers ranges between 28% to as high as 70% [3,4,37]. Even if the lowest estimate of 28% prevalence is the most accurate, this still represents a significant number of patients that may benefit from E2 treatment.…”

Protein kinase C and cancer: what we know and what we do not

“…Gö6976, a pharmacological inhibitor of cPKCs [43], abrogates ErbB2-mediated up-regulation of urokinase-type plasminogen activator (uPA) and cell invasion [44]. Whereas PKCα expression is higher in triple-negative breast cancers than to other subtypes [45], we still need to underscore meaningful associations of this PKC with genetic alterations specific for each breast cancer subtype.…”

Protein Kinase C (PKC) Isozymes and Cancer

“…Further, research has indicated that PKC may be a critical factor in breast cancer antiestrogen resistance. PKC and ER expression are inversely related [47] and PKC is positively correlated with triple-negative breast cancers, which show no expression of ERs, progesterone receptors, or ErbB2 [50,51]. Breast cancer cells with overexpression of PKC also show high resistance for TAM treatment and hormone (e.g., estrogen)-independent growth [52][53][54][55], but inhibition of PKC induces TAM sensitivity [53][54][55].…”