Abstract 2092: Elevated PKCα expression and its association with Notch signaling in localized and metastatic prostate cancers

Abstract

Abstract Background: Conventional protein Kinase C alpha (PKCα) is linked to the regulation of cell proliferation, differentiation, motility, survival, and apoptosis. Elevated PKCα expression has been reported in human early prostate cancer (PCa) and rat prostatic tumor cell lines. In this study, the expression level of PKCα was evaluated by immunohistochemistry (IHC) and correlated with the expression levels of Notch1 and Jagged1 in localized and metastatic PCa. Methods: : IHC for PKCα was performed on tissue microarray (TMA) slides containing 156 formalin-fixed and paraffin-embedded (FFPE) prostatic tissues specimens, including 39 benign prostatic changes, 97 localized prostate cancers and 20 metastatic prostate cancers. The expression level of PKCα was reported as a final IHC score calculated as staining extent score (0-3) multiplied by intensity score (0-3) with a maximal score of 9. ANOVA was employed to reveal the differences in IHC scores among pathologic categories, followed by Tukey-adjusted pairwise comparisons. Spearman correlation coefficient was evaluated to measure correlation between expression levels of PKCα, Notch1, and Jagged1. Results: IHC staining for PKCα was predominantly observed in cytoplasm (in 94% specimens). The score of PKCα cytoplasmic staining in metastatic PCa (5.48 ± 1.84, Mean ±SD) was significantly higher than those in localized PCa (3.30 ± 2.10, P = 2.95E-05) and in benign prostatic tissue (1.92 ± 1.53, P = 6.45E-09). Similarly, IHC score in localized PCa was significantly higher than that observed in benign prostatic changes (P = 0.001). Correlation analysis revealed that the expression level of cytoplasmic PKCα was significantly correlated with the expression levels of cytoplasmic Notch1 (r = 0.396, P = 5.85E-05), cytoplasmic Jagged1 (r = 0.610, P = 3.42E-11), and membranous Jagged1 (r = 0.354, P = 3.76E-04, respectively) in localized and metastatic prostate cancers. Conclusions: Our results indicate that up-regulation of PKCα plays a role not only in PCa formation and progression, but also in PCa metastasis. The evidence of significant correlation between PKCα and Jagged1-Notch1 signaling pathway supports the notion that synergy of PKCα with Jagged1-Notch1 signaling may play an important role in modulating the tumorgenesis and metastasis in human PCa. Citation Format: Xinchun Zhou, He Zhu, Xu Zhang, Jack Lewin, Lucio Miele. Elevated PKCα expression and its association with Notch signaling in localized and metastatic prostate cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2092. doi:10.1158/1538-7445.AM2014-2092