P53 downregulates the gene expression of mitochondrial aconitase in human prostate carcinoma cells

Ke Hung Tsui, Tsui Hsia Feng, Yu Fen Lin, Phei Lang Chang, Horng Heng Juang

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


Background Mitochondrial aconitase (mACON) is regarded as the key enzyme in citrate oxidation in human prostate epithelial cells, and its abnormal expression has been implicated in tumorigenesis of the prostate. Evidence also supports a broad role for the p53 gene in suppressing prostatic tumorigenesis. We investigated whether p53 regulates mACON expression and explore the potential mechanisms responsible for its effect on prostate cancer cells. Methods Camptothecin (CPT) treatments and transient overexpression of p53 were used to investigate p53 regulation of mACON and may effects were assessed using immunoblotting and transient gene expression assays. Results In vitro enzymatic activity assays and immunoblot assays showed that CPT treatment induced p53 expression while reducing mACON protein biosynthesis in wild-type p53 expressing LNCaP cells. Immunoblot assays and reporter assays revealed that transient transfection of a p53 expression vector into p53-null PC-3 cells decreased mACON expression. Cyclic pifithrin-α, an inhibitor of p53 transcriptional activity, blocked the decrease in mACON gene expression resulting from CPT treatment in LNCaP cells. Two putative p53 response elements were identified within the mACON promoter; however, mutation of these putative p53 response elements did not abolish the effect of CPT whereby it decreased mACON expression. A similar result was obtained for the effect of these mutants on the promoter activity of the mACON gene after transient overexpression of p53. Conclusions Together these results suggest that p53 downregulation of mACON gene expression in human prostate carcinoma cells may not occur through the putative consensus p53 response elements found within the mACON promoter.

Original languageEnglish
Pages (from-to)62-70
Number of pages9
Issue number1
Publication statusPublished - Jan 1 2011
Externally publishedYes


  • camptothecin
  • LNCaP
  • mACON
  • p53
  • PC-3
  • pifithrin-α
  • promoter
  • prostate

ASJC Scopus subject areas

  • Oncology
  • Urology


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