| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
Although a dramatic surge has occurred on studies defining the role of cyclooxygenase COX-2 and the product prostaglandins (PGs) in causation and prevention of cancer, the correlation of PG metabolic clearance pathway with cancer has never been investigated yet. The expression levels of genes for prostaglandin synthesis (COX-1, COX-2), genes for prostaglandin metabolic clearance (the prostaglandin transporter PGT and 15 hydroxyprostaglandin dehydrogenase PGDH) and EP receptors (EP1-EP4) were quantified by means of real-time PCR based on SYBR Green I dye detection in several human prostate cancer cell lines (LNCaP, DU145, and PC3 cells), a human prostate normal epithelial cell line (PrEC), human prostate biopsy specimens, human bladder cancer specimens, and human renal cancer specimens. BPH epithelial cells in prostate biopsy specimens, normal bladder mucosal epithelial cells, and normal tubule cells were captured as a control to each cancer cell from the same specimen using a technique
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of laser capture microdissection. PGT mRNA expression was significantly down-regulated to 20% on the one hand, and PGDH was up-regulated to 258-folds higher on the other in PC3 cells (p< 0.001), LNCaP cultured with dehydrotestosterone (p<0.01 and p<0.05, respectively), compared to those in PrEC. In contrast, PGDH was remarkably down-regulated to 5% in DU145 cell with significant reduction of PGT expression (p<0.001 and p<0.05, respectively). There was the same fashion of the expression of PGT and PGDH as PC3 in prostate biopsy specimens and bladder cancer specimens. COX-1 and COX-2 expressions were not detected in cancer cell lines, while not significant in specimen tissue. The expression profiles of EP receptors were unique to each cancer. CONCLUSIONS: The differential expression of prostaglandin metabolic clearance genes make specific prostaglandin environment, that may be involved in controlling cancer causation, preservation and apoptosis via intracellular or extracellular specific receptors. Less
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