Nucleolin regulates c-Jun/Sp1-dependent transcriptional activation of cPLA2 in phorbol ester-treated non-small cell lung cancer A549 cells
| Autor: | Ben Kuen Chen, Liang Yi Hung, Jen-Hui Tsou, Wen Chang Chang, Wu Chou Su, Wei Chiao Wang, Kwang Yu Chang, Joseph T. Tseng |
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| Rok vydání: | 2007 |
| Předmět: |
Transcriptional Activation
Small interfering RNA Lung Neoplasms Transcription Genetic Proto-Oncogene Proteins c-jun Sp1 Transcription Factor Biology Carcinoma Non-Small-Cell Lung Cell Line Tumor Gene expression Genetics Transcriptional regulation Humans Promoter Regions Genetic Molecular Biology Transcription factor Group IV Phospholipases A2 c-jun RNA-Binding Proteins Promoter Phosphoproteins Molecular biology GC Rich Sequence Gene Expression Regulation Neoplastic Tetradecanoylphorbol Acetate Signal transduction Nucleolin Transcription Factors |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkm1027 |
| Popis: | The expression of cPLA2 is critical for transformed growth of non-small cell lung cancer (NSCLC). It is known that phorbol 12-myristate 13-acetate (PMA)-activated signal transduction pathway is thought to be involved in the oncogene action in NSCLC and enzymatic activation of cPLA2. However, the transcriptional regulation of cPLA2alpha in PMA-activated NSCLC is not clear. In this study, we found that PMA induced the mRNA level and protein expression of cPLA2alpha. In addition, two Sp1-binding sites of cPLA2alpha promoter were required for response to PMA and c-Jun overexpression. Small interfering RNA (siRNA) of c-Jun and nucleolin inhibited PMA induced the promoter activity and protein expression of cPLA2alpha. Furthermore, PMA stimulated the formation of c-Jun/Sp1 and c-Jun/nucleolin complexes as well as the binding of these transcription factor complexes to the cPLA2alpha promoter. Although Sp1-binding sites were required for the bindings of Sp1 and nucleolin to the promoter, the binding of nucleolin or Sp1 to the promoter was independent of each other. Our results revealed that c-Jun/nucleolin and c-Jun/Sp1 complexes play an important role in PMA-regulated cPLA2alpha gene expression. It is likely that nucleolin binding at place of Sp1 on gene promoter could also mediate the regulation of c-Jun/Sp1-activated genes. |
| Databáze: | OpenAIRE |
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