p53 and its co-activator p300 are inversely regulated in the mouse colon in response to carcinogen

Toxicol Lett. 2003 Sep 30;144(2):213-24. doi: 10.1016/s0378-4274(03)00221-2.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Carcinogens / toxicity*
  • Cells, Cultured
  • Colon / drug effects
  • Colon / metabolism*
  • Colonic Neoplasms / chemically induced*
  • Colonic Neoplasms / pathology
  • DNA Damage
  • E1A-Associated p300 Protein
  • Epithelial Cells / chemistry
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, p53 / genetics*
  • Immunoblotting
  • Immunohistochemistry
  • Mice
  • Mice, Inbred A
  • Nuclear Proteins / genetics*
  • Nuclease Protection Assays
  • Proteins / chemistry
  • Proteins / isolation & purification
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / isolation & purification
  • Trans-Activators / genetics*
  • Transcriptional Activation
  • bcl-2-Associated X Protein

Substances

  • Bax protein, mouse
  • Carcinogens
  • Nuclear Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Trans-Activators
  • bcl-2-Associated X Protein
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse