p53 and its co-activator p300 are inversely regulated in the mouse colon in response to carcinogen.
We examined the p53 response following acute exposure of mice to the colon-specific carcinogen azoxymethane (AOM). No overall induction of p53-regulated genes was observed in the mouse colon, and only a small subpopulation of apoptotic colonocytes showed increased Bax staining. In contrast, the liver showed dramatic increases in p53-regulated gene expression. Subdued p53 gene activation in the colon did not appear to result from a lack of p53 stabilization, but did correspond to a drop in the expression of its transcriptional co-activator, p300. We propose that inefficient gene activation by p53 in the colon contributes to the organotrophic effects of AOM.
Aizu
Wataru
W
Department of Molecular and Cell Biology, University of Connecticut, 75 North Eagleville Road, U-3125, Storrs, CT 06269, USA.
Guda
Kishore
K
Nambiar
Prashant
P
Xin
Tong
T
Thibodeau
Michael
M
Rosenberg
Daniel W
DW
Giardina
Charles
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004249:DNA Damage; D050881:E1A-Associated p300 Protein; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016158:Genes, p53 / Q000235:genetics*; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008805:Mice, Inbred A; D009687:Nuclear Proteins / Q000235:genetics*; D023282:Nuclease Protection Assays; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D002273:Carcinogens; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D015534:Trans-Activators; D051028:bcl-2-Associated X Protein; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse