Nucleolin regulates c-Jun/Sp1-dependent transcriptional activation of cPLA2α in phorbol ester-treated non-small cell lung cancer A549 cells

Jen Hui Tsou, Kwang Yu Chang, Wei Chiao Wang, Joseph T. Tseng, Wu Chou Su, Liang Yi Hung, Wen Chang Chang, Ben Kuen Chen

研究成果: 雜誌貢獻文章同行評審

35 引文 斯高帕斯(Scopus)

摘要

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 cPLA2α in PMA-activated NSCLC is not clear. In this study, we found that PMA induced the mRNA level and protein expression of cPLA2α. In addition, two Sp1-binding sites of cPLA2α 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 cPLA2α. 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 cPLA2α 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 cPLA2α 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.

原文英語
頁(從 - 到)217-227
頁數11
期刊Nucleic Acids Research
36
發行號1
DOIs
出版狀態已發佈 - 一月 2008
對外發佈

ASJC Scopus subject areas

  • 遺傳學

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