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Transcription coactivator PBP/MED1 is required for diethylnitrosamine‐induced hepatocarcinogenesis in the mouse
Author(s) -
Matsumoto kojiro,
Jia Yuzhi,
Viswakarma Navin,
Rao M Sambasiva,
Reddy Janardan K
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.927.9
Subject(s) - coactivator , carcinogenesis , biology , cancer research , transcription factor , nuclear receptor , endocrinology , gene , genetics
Nuclear receptor coactivator PBP (peroxisome proliferator‐activated receptor (PPAR)‐binding protein/MED1) functions as an anchor for mediator multisubunit cofactor transcription complex. Disruption of this gene in the mouse results in embryonic lethality. Using PBP liver conditional null (PBPΔ Liv ) mice, we reported that PBP is essential for PPARα ligand, Wy‐14,643‐induced liver tumorigenesis. We now examined the role of PBP in diethylnitrosamine‐initiated/phenobarbital promoted liver tumor induction. PBPΔ Liv mice subjected to this protocol for 1, 4, and 12 weeks, revealed a striking proliferative response and clonal expansion of few residual PBP positive hepatocytes. No proliferative expansion of PBP null hepatocytes was noted. Liver tumors developed in wild‐type and PBPΔ Liv mice after 1 year treatment but all hepatocellular carcinomas that developed in PBPΔ Liv mice were PBP positive although the surrounding non‐tumor portions of liver in PBPΔ Liv mice did not express PBP. These data indicate that PBP is essential for the development of hepatocellular carcinoma. (This work was supported by NIH Grant DK083163).