期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2009
卷号:106
期号:49
页码:20859-20864
DOI:10.1073/pnas.0911351106
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Glutathione transferases are a multigene family of proteins that catalyze the conjugation of toxic electrophiles and carcinogens to glutathione. Glutathione transferase Pi (GSTP) is commonly overexpressed in human tumors and there is emerging evidence that the enzyme has additional cellular functions in addition to its role in drug and carcinogen detoxification. To investigate the unique functions of this enzyme, we have crossed Gstp null mice with an initiated model of colon cancer, the ApcMin mouse. In contrast to the ApcMin/+ Gstp1/p2+/+ (Gstp-wt ApcMin) mice, which rarely develop colonic tumours, ApcMin/+Gstp1/p2-/- (Gstp-null ApcMin) mice had a 6-fold increase in colon adenoma incidence, and a 50-fold increase in colorectal adenoma multiplicity, relative to Gstp-wt ApcMin. This increase was associated with early tumor onset and decreased survival. Analysis of the biochemical changes in the colon tissue of Gstp-null ApcMin mice demonstrated a marked induction of many inflammatory genes, including IL-6, IL-4, IFN-{gamma