TY - JOUR
T1 - Regulation of the human cathepsin E gene by the constitutive androstane receptor
AU - Page, Jeanine L.
AU - Strom, Stephen C.
AU - Omiecinski, Curtis J.
N1 - Funding Information:
The authors are grateful for the expert technical assistance of Mary Johnson-Hutchinson and Denise Weyant. This study was supported by USPHS Grants from the NIGMS, GM66411, and by the Liver Tissue Procurement and Distribution System, under NIH Contract NO1-DK-9-2310.
PY - 2007/11/1
Y1 - 2007/11/1
N2 - Cathepsin E (CTSE) is an aspartic protease that has been linked to antigen processing and innate immunity. Elevated levels of CTSE expression have also been associated with several forms of cancer, including carcinomas exhibiting highly invasive character. In this study, we performed DNA microarray experiments, together with quantitative reverse transcriptase PCR analyses and enzymatic activity determinations to identify human CTSE as a novel target gene for regulation by the constitutive androstane receptor (CAR), a nuclear receptor activated by the liver tumor promoting agent, phenobarbital. In particular, two motifs within the 5′-flanking region of the human CTSE gene were identified as direct sites of interaction with CAR/RXRα heterodimers, a direct repeat-3 site at position -766 and a direct repeat-4 site at position -1407. Thus, these studies demonstrate CAR-mediated regulation of CTSE within primary hepatocyte cultures from several individual donors and suggest that elevated CTSE activity may play a functional role in the etiology of hepatocarcinogenesis.
AB - Cathepsin E (CTSE) is an aspartic protease that has been linked to antigen processing and innate immunity. Elevated levels of CTSE expression have also been associated with several forms of cancer, including carcinomas exhibiting highly invasive character. In this study, we performed DNA microarray experiments, together with quantitative reverse transcriptase PCR analyses and enzymatic activity determinations to identify human CTSE as a novel target gene for regulation by the constitutive androstane receptor (CAR), a nuclear receptor activated by the liver tumor promoting agent, phenobarbital. In particular, two motifs within the 5′-flanking region of the human CTSE gene were identified as direct sites of interaction with CAR/RXRα heterodimers, a direct repeat-3 site at position -766 and a direct repeat-4 site at position -1407. Thus, these studies demonstrate CAR-mediated regulation of CTSE within primary hepatocyte cultures from several individual donors and suggest that elevated CTSE activity may play a functional role in the etiology of hepatocarcinogenesis.
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U2 - 10.1016/j.abb.2007.08.001
DO - 10.1016/j.abb.2007.08.001
M3 - Article
C2 - 17888866
AN - SCOPUS:35448976355
SN - 0003-9861
VL - 467
SP - 132
EP - 138
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1
ER -