How do the Cox inhibitors inhibit or prevent the development of tumors?
15-Lipoxygenase-1 expression is altered in human colorectal tumors and is induced by histone deacetylase inhibitors in human colorectal cells with a corresponding decrease in cell growth and induction of apoptosis. Based data obtained from xenograph mouse models, 15-Lox-1 acts as a tumor suppressor. Recently, the group found 15-Lox-1 to increase the activation of p53 by increasing the phosphorylation at serine 15. As a result the expression of the many down stream targets genes of p53 are increased. Currently, group members are investigating the interaction between the kinases that phosphorylated p53 and 15-Lox-1 to determine the mechanisms responsible. To study how Cox-2 participates in tumor development and progression, the group has developed a Cox-2-Cre-Lox-P mouse that can be breed to produce tissue specific Cox-2 expression. Initially we generated a mouse with ubiquitous Cox-2 expression that proved to be fatal to the offspring. The mice had several malformations and appeared to
