Overexpression of p53 Inhibits Promoter Activity of NKX3.1 Gene

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Chinese Journal of Biochemistry and Molecular Biology ›› 2007, Vol. 23 ›› Issue (07) : 560-565.

Research Papers

Overexpression of p53 Inhibits Promoter Activity of NKX3.1 Gene

YU Chun-Xiao¹⁾, LIU Wen-Wen¹⁾, WU Wei-Fang¹⁾,CHEN Wei-Wen¹⁾, ZHANG Peng-Ju¹⁾,　ZHANG Qi²⁾, JIANG An-Li^1)*，ZHANG Jian-Ye^1)*

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Abstract

Homeogene NKX3.1is specially expressed in prostate and plays an important role in the development and growth of prostate cancer, while the mutation of p53 often occurs during the development of prostate cancer. In order to study the relationship between p53 and NKX3.1 in prostate cancer cells, the recombinant plasmid (pGL3-1040) of NKX3.1 promoter (1 040 bp)-luciferase reporter gene and its mutants were constructed and transiently transfected into prostate cancer cell LNCaP to analyze the effects of p53 overexpression on NKX3.1 promoter activity by using luciferase reporter assay. Our results showed that p53 overexpression inhibited NKX3.1 promoter activity and decreased NKX3.1expression in LNCaP cells. Analysis by TRANSFAC database indicated that a p53 responsive element (5′half site) was located in the region from -526 to -507 in the upstream of NKX3/1 gene. But the deletion of the core sequence of p53 responsive element from the NKX3.1 promoter did not abrogate the p53-mediated repression of the NKX3.1 promoter activity, suggesting that inhibition of p53 on the NKX3.1promoter was not achieved by binding to p53 responsive element. Furthermore, the results of 5′ deletion mutation analysis found that the region of the NKX3.1 promoter between the -140～+8 bp in the upstream of the NKX3.1 gene was negatively regulated by p53. The analysis showed that there were a Sp1 and a CREB elements within the region of -140～+8 bp. The results of transient transfection with Sp1 or CREB expression plasmid demonstrated that p53 also did not inhibit the NKX3.1 promoter by interaction with Sp1 or CREB. Although these results indicated that p53 overexpression was capable to inhibit the NKX3.1 promoter activity and downregulate the NKX3.1 gene expression, further studies would need to explore the mechanisms.

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NKX3.1 / promoter / p53 / negative regulation

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YUChun-Xiao,LIUWen-Wen,WUWei-Fang,CHENWei-Wen,ZHANGPeng-Ju,ZHANGQi,JIANGAn-Li，ZHANGJian-Ye. Overexpression of p53 Inhibits Promoter Activity of NKX3.1 Gene[J]. Chinese Journal of Biochemistry and Molecular Biology, 2007, 23(07): 560-565

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Received	Revised	Published
2007-01-03	1900-01-01	2007-07-20
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2007-07-20

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