Eicosanoid Regulation of Prostate Cancer Progression: Disruption of Hemidesmosomes and Collaboration in Tumor Invasive Growth
Annual rept. 1 Mar 2004-28 Feb 2005
WAYNE STATE UNIV DETROIT MI
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A significant achievement in the current reporting period is our ability to immunostain both the 12-LOX protein and 4 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 4 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 4 integrin shows strong interaction with 12-LOX. An important observation is that the full-length cytoplasmic tail of 4 integrin, when expressed ectopically, disrupts the interaction with 12-LOX with 4 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 nunu mice.
- Anatomy and Physiology
- Medicine and Medical Research