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

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)217-227
Number of pages11
JournalNucleic Acids Research
Volume36
Issue number1
DOIs
Publication statusPublished - Jan 2008
Externally publishedYes

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Phorbol Esters
Non-Small Cell Lung Carcinoma
Transcriptional Activation
Acetates
Binding Sites
nucleolin
A549 Cells
phorbol-12-myristate
Oncogenes
Small Interfering RNA
Genes
Signal Transduction
Proteins
Transcription Factors
Gene Expression
Messenger RNA
Growth

ASJC Scopus subject areas

  • Genetics

Cite this

Nucleolin regulates c-Jun/Sp1-dependent transcriptional activation of cPLA2α in phorbol ester-treated non-small cell lung cancer A549 cells. / Tsou, Jen Hui; Chang, Kwang Yu; Wang, Wei Chiao; Tseng, Joseph T.; Su, Wu Chou; Hung, Liang Yi; Chang, Wen Chang; Chen, Ben Kuen.

In: Nucleic Acids Research, Vol. 36, No. 1, 01.2008, p. 217-227.

Research output: Contribution to journalArticle

Tsou, Jen Hui ; Chang, Kwang Yu ; Wang, Wei Chiao ; Tseng, Joseph T. ; Su, Wu Chou ; Hung, Liang Yi ; Chang, Wen Chang ; Chen, Ben Kuen. / Nucleolin regulates c-Jun/Sp1-dependent transcriptional activation of cPLA2α in phorbol ester-treated non-small cell lung cancer A549 cells. In: Nucleic Acids Research. 2008 ; Vol. 36, No. 1. pp. 217-227.
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abstract = "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.",
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