Abstract 2369: Transcription activators that regulate PKC-iota expression and are downstream targets of PKC-iota

Abstract

Abstract Protein Kinase C-iota (PKC-iota) is an anti-apoptotic oncogene over-expressed in multiple cancers including prostate, ovarian, and glioma. PKC-iota is part of a cycle that helps cancer cell avoid senescence by releasing the transcription factor NFkB and promoting apoptotic resistance. PKC-iota is activated externally by factors like loss of PTEN (Paget 2012). However, while under the effect PKC-iota specific inhibitors, expression levels decreased, suggesting PKC-iota plays a role in regulating its own expression. A previous study showed the ELK1 transcription factor to be a regulator of PKC-iota (Gustafson 2003). Other transcription factors including Jun, ISGF3, PAX3, EGR1, and FOXO1 bind on or near the promoter sequence of the gene and their role in PKC-iota regulation was analyzed. Each transcription factor was systematically silenced with its own siRNA. Western Blotting revealed expression of PKC-iota in the transcription factor silenced cells determining which transcription factors are key players in regulation of PKC-iota. qPCR and microarray were performed to analyze the transcriptome of treated cells to match protein levels with mRNA levels. Targets both up and downstream of PKC-iota were analyzed to find the pathway that PKC-iota uses to help regulate itself. Citation Format: Andre H. Apostolatos, Wishrawana S. Ratnayake, Tracess Smalley, Anisul Islam, Mildred Acevedo-Duncan. Transcription activators that regulate PKC-iota expression and are downstream targets of PKC-iota [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2369. doi:10.1158/1538-7445.AM2017-2369