Nucleolin regulates c-Jun/Sp1-dependent transcriptional activation of cPLA2alpha in phorbol ester-treated non-small cell lung cancer A549 cells.
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.
Tsou
Jen-Hui
JH
Department of Pharmacology, National Cheng Kung University, Tainan 701, Taiwan.
Chang
Kwang-Yu
KY
Wang
Wei-Chiao
WC
Tseng
Joseph T
JT
Su
Wu-Chou
WC
Hung
Liang-Yi
LY
Chang
Wen-Chang
WC
Chen
Ben-Kuen
BK
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D020862:GC Rich Sequence; D015972:Gene Expression Regulation, Neoplastic; D054513:Group IV Phospholipases A2 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D000097796:Nucleolin
D054513:Group IV Phospholipases A2; D010750:Phosphoproteins; D016755:Proto-Oncogene Proteins c-jun; D016601:RNA-Binding Proteins; D016329:Sp1 Transcription Factor; D013755:Tetradecanoylphorbol Acetate; D014157:Transcription Factors; D000097796:Nucleolin