PKCalpha expression regulated by Elk-1 and MZF-1 in human HCC cells.
Our previous study found that PKCalpha was highly expressed in the poor-differentiated human HCC cells and associated with cell migration and invasion. In this study, we further investigated the gene regulation of this enzyme. We showed that PKCalpha expression enhancement in the poor-differentiated human HCC cells was found neither by DNA amplification 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 PKCalpha promoters, only Elk-1 and MZF-1 antisense oligonucleotide showed a significant reduction in the PKCalpha mRNA level. They also reduced cell proliferation, cell migratory and invasive capabilities, and DNA binding activities in the PKCalpha promoter region. Over-expression assay confirmed that the PKCalpha expression may be modulated by these two factors at the transcriptional level. Therefore, these results may provide a novel mechanism for PKCalpha expression regulation in human HCC cells.
Hsieh
Yi-Hsien
YH
Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
Wu
Trang-Tiau
TT
Tsai
Jen-Hsiang
JH
Huang
Chih-Yang
CY
Hsieh
Yih-Shou
YS
Liu
Jer-Yuh
JY
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005784:Gene Amplification; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D009361:Neoplasm Invasiveness; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; C085969:MZF1 protein, human; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D051571:Protein Kinase C-alpha