Eicosanoid Regulation of Prostate Cancer Progression: Disruption of Hemidesmosomes and Collaboration in Tumor Invasive Growth; Final rept. 1 Mar 2003-28 Feb 2006

摘要

A significant achievement in the current reporting period is our ability to immunostain both the 12-LOX protein and Beta4 integrin in paraffin- embedded prostate tumor tissues circumventing the problems described in the previous report. With the new protocol we have stained about 20 cases so far and the remaining cases are in progress. We have generated several stable transfectants of PC-3 cells expressing mutant forms of the Beta4 integrin and studied their interaction with 12-LOX. During this study we have identified that the peptide spanning between amino acids 1126 and 1315 of the cytoplasmic tail of the Beta4 integrin shows strong interaction with 12-LOX. An important observation is that the full-length cytoplasmic tail of Beta4 integrin when expressed ectopically disrupts the interaction with 12-LOX with Beta4 integrin in a dominant negative manner. This interaction also resulted in a decrease in the biosynthesis of the enzymatic product 12-HETE as well as reduction in the tumor growth rate from subcutaneously injected PC-3 cells in athymic nu/nu mice.