Our previous Study found that PKC alpha was highly expressed in the poor-differentiated human HCC cells and associated with cell rnigration and invasion. In this study, we further investigated the gene regulation of this enzyme. We showed that PKC alpha expression enhancement in the poor-differentiated human HCC cells Was found neither by DNA ainplification nor by increasing mRNA stability Using differential PCR and mRNA decay assays. After screening seven transcription factors in the putative cis-acting regulatory elements Of human PKC alpha promoters, only Elk-1 and MZF-1 antisense oligonucleotide showed a significant reduction in the PKC alpha. mRNA level. They also reduced cell proliferation, cell migratory and invasive capabilities, and DNA binding activities in the PKCa promoter region. Over-expression assay confirmed that the PKC alpha expression may be modulated by these two factors at the transcriptional level. Therefore, these results may provide a novel mechanisin for PKC alpha expression regulation in human HCC Cells. (c) 2005 Elsevier Inc. All rights reserved.