Abstract 799: Global genomic analysis identified PRKCI as a potential therapeutic target gene for human clear cell ovarian cancer.

Clear cell ovarian cancer (CCOC), a rare epithelial ovarian cancer histotype, is more resistant to standard chemotherapy and has a worse prognosis than serous and endometrioid histotypes. We attempted to identify genes that are responsible for the aggressive behavior of CCOC and could be potential therapeutic targets using genomic and expression profilings. To identify gene amplification, genome-wide DNA copy number alterations were measured in 13 CCOC cell lines using high-resolution oligonucleotide array CGH (Agilent 105k Human Genome CGH Microarray). GISTIC analysis identified 16 amplified regions containing 391 genes. After comparison to our database of differentially expressed genes between human CCOC specimens and normal ovarian surface epithelium specimen (Affymetrix U133 Plus 2.0 microarrays), 45 of the amplified genes showed mRNA overexpression in CCOC specimens. Among the 45 genes, protein kinase C iota (PRKCI) was amplified in 9/13 CCOC cell lines and was overexpressed (6.7 fold) in CCOC specimens. Analysis using PathwayStudio software identified PRKCI mediated pathways for cell migration and invasion. Knock-down of PRKCI by transfection with PRKCI specific siRNAs suppressed cell migration and invasion in KOC-7c and OVISE cells. On the other hand, ectopic expression of PRKCI by transfection with PRKCI expressing vector enhanced cell migration and invasion in ES2 and TOV21G cells. The results from the present study therefore suggested that PRKCI may promote metastasis and serve as a potential target gene for treatment of human clear cell ovarian cancer. Citation Format: Tsun Yee Tsang, Gayatry Mohapatra, Hiroaki Itamochi, Samuel C. Mok, Michael J. Birrer. Global genomic analysis identified PRKCI as a potential therapeutic target gene for human clear cell ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 799. doi:10.1158/1538-7445.AM2013-799