Article

Pre-B-cell leukemia transcription factor 1 regulates expression of valosin-containing protein, a gene involved in cancer growth.

Department of Pathology, Medical School of Tongji University, Shanghai, China.
American Journal Of Pathology (impact factor: 4.89). 02/2007; 170(1):152-9. DOI:10.2353/ajpath.2007.060722 pp.152-9
Source: PubMed

ABSTRACT Valosin-containing protein (VCP) is involved in a wide variety of cellular functions. Our previous studies showed that the enhanced expression of VCP in cancer cells correlated with invasion and metastasis of cancers. Here, the regulatory mechanism for VCP transcription was investigated. Luciferase reporter constructs containing serially deleted 5'-flanking region of the VCP gene were transfected into MCF7 mammary carcinoma cell line, in which VCP was abundantly expressed. The deletion and mutation at the two binding motifs for pre-B-cell leukemia transcription factor 1 (PBX1) reduced the luciferase activity, indicating that these two PBX1 motifs mediated the transactivation of the VCP gene. Chromatin immunoprecipitation assay showed the binding of PBX-1 to the 5'-flanking region of the VCP gene. The knockdown of PBX1 by siRNA decreased the expression level of VCP. VCP is reported to maintain cell viability after the treatment of tumor necrosis factor-alpha. The viability of tumor necrosis factor-alpha-treated cells was significantly reduced in PBX1 knockdown MCF7. These findings indicate that PBX1 plays a crucial role in VCP expression and function and that the PBX-VCP pathway might be important for cell survival under cytokine stress.

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Keywords

5'-flanking region
 
cancer cells correlated
 
Chromatin immunoprecipitation assay
 
crucial role
 
cytokine stress
 
luciferase activity
 
Luciferase reporter constructs
 
PBX-VCP pathway
 
PBX1 knockdown MCF7
 
previous studies
 
serially deleted 5'-flanking region
 
tumor necrosis factor-alpha
 
tumor necrosis factor-alpha-treated cells
 
two binding motifs
 
two PBX1 motifs
 
Valosin-containing protein
 
VCP expression
 
VCP gene
 
VCP transcription
 
wide variety