Eicosanoid Regulation of Prostate Cancer Progression: Disruption of Hemidesmosomes and Collaboration in Tumor Invasive Growth
Abstract
During the progression of human PCa, hemidesmosomes are lost. Hemidesmosomes are adhesion structures that anchor epithelial cells to basement membrane and function as a tumor suppressor. We found that 12-lipoxygenase directly interacts with beta4 integrin. We hypothesize that an increase in 12-LOX activity can cause the disassembly of hemidesmosomes, mobilization of alpha6beta4 integrin from hemidesmosomes to other parts of the cell membrane, and stimulate tumor invasive growth. We proposed to conduct a correlation study using clinical tumor specimens. We will study whether 12(S)-HETE can disrupt hemidesmosomes and whether 12-LOX inhibitors promote the formation of hemidesmosomes. Then we will study the underlying signaling pathway, especially PKCalpha, initiated by 12(S)-HETE, in the disassembly of hemidesmosomes. Next we will overexpress beta4 integrin and study the role of the interaction between 12-LOX and beta4 integrin in the adhesion, proliferation, migration, and survival, in response to HGF/SF. Finally we will xenograft these transfected cells into mice, to evaluate whether any phenotypic changes of tumor cells in vitro can be recapitulated in vivo. The work will significantly advance our understanding about the complex process of prostate cancer progression as well as the possible role played by dietary fat in the progression of prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2004
- Accession Number
- ADA427877
Entities
People
- Kenneth V. Honn
Organizations
- Wayne State University