E2F3a is a transcription factor that has been shown to be overexpressed in liver cancer tissues. To characterize the function of E2F3a in hepatocellular carcinoma (HCC), effects of ectopic overexpression of E2F3a on cell cycle, apoptosis, and gene expression of HepG2 cells were studied. E2F3a significantly enhances the apoptotic rate of HepG2 cells by 33% but only has minor effects on cell proliferation. By using microarray analyses, we identified 162 target genes (160 upregulated and 2 downregulated) of the E2F3a. Differential expression of 11 genes was further confirmed by real-time PCR. Eight of these 11 genes, including XAF1, CEACAM1, STAT1, ATF3, TNFSF10, KLF6, CLDN1, and TAP1, were confirmed to be upregulated by more than twofold. Functional enrichments of differentially expressed genes retrieved 21 apoptosis-related genes and 32 transcriptional regulation-related genes. These results suggest that E2F3a induces apoptosis in HepG2 cells and plays important roles in regulating transcription. Finally, positive correlation was found between E2F3a and CEACAM1 mRNA levels in clinically well-differentiated human HCC specimens.
Copyright © 2010 Wiley-Liss, Inc.