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MedicineAnatomy and Physiology

Eicosanoid Regulation of Prostate Cancer Progression: Disruption of Hemidesmosomes and Collaboration in Tumor Invasive Growth

Authors: Kenneth V. Honn; Daotai Nei; Keqin Tang; Mario Lamberti; WAYNE STATE UNIV DETROIT MI
Abstract:
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 nu/nu mice.

Limitations: APPROVED FOR PUBLIC RELEASE
Description: Annual rept. 1 Mar 2004-28 Feb 2005
Pages: 10
Report Date: MAR 2005
Contract Number: DAMD170310102
Report Number: A332464
Keywords relating to this report:
*Cytoplasm
*EICOSANE
*GROWTH(PHYSIOLOGY)
*GROWTH_PHYSIOLOGY_
*PROSTATE CANCER
BIOSYNTHESIS
EMBEDDING
ENZYMES
MICE
MUTATIONS
NEOPLASMS
PEPTIDES
PROSTATE GLAND
TAIL ASSEMBLIES
TISSUES_BIOLOGY_
WAXES
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