Korean J Urol.  2004 May;45(5):478-484.

Prostagladin E Receptor II and IV Increase the Expression of Martrix Metalloproteinase-7 in PC (Prostate Cancer)-3 Cells

• Kim TH
• Kim YS
• Myoung SC
• Lee JH
• Won EH

Abstract

PURPOSE: The effects of PGE2 receptors (EP1, 2, 3, 4) on the proliferation of prostate cancer cells are still unclear. The degradation of the basement membrane by MMP-2, 7, 9 and TIMP-1, 2 is a critical point in tumor invasion and metastasis. We investigated the effects of PGE2 receptors concerning MMP and TIMP after the treatment of COX-2 inhibitors on prostate cancer cell-lines.
MATERIALS AND METHODS
Two prostate cancer cell-lines, PC-3 and DU-145 cells were used in this study. RT-PCR were performed to detect the mRNA expression of EP1, 2, 3, 4, MMP-2, 7, 9 and TIMP-1, 2, MMP-7 was measured by ELISA after being treated with the selective EP2 agonist and EP4 agonist 10(-10), 10(-8), 10(-6) microM respectively.
RESULTS
EP2, 3 and 4 mRNA were expressed in both cell-lines. After the NS-398 treatment, EP2 and EP4 mRNA expressions decreased in PC-3 cells. While only the MMP-7 mRNA expression decreased in PC-3 cells after NS-398 treatment, after NS-398 with selective EP2 agonist and EP4 agonist, MMP-7 mRNA expression increased. In PC-3 cells, selective EP2 agonist and EP4 agonist induced a significant dose-dependent increase in MMP-7 production in comparison to the NS-398 treatment group (control) in the conditioned ELISA medium.
CONCLUSIONS
These results strongly suggest that COX-2, to some extent, contribute to prostate carcinogenesis at the EP2 and EP4 receptor, which could also be explained by increments of MMP-7 in PC-3 cells. Therefore, these findings show that selective EP inhibitor is useful in preventing specific disease progression in prostate cancer.

Keyword

Prostate cancer; Cyclooxygenase; PGE2 receptor; Matrilysin

MeSH Terms

Basement Membrane
Carcinogenesis
Cyclooxygenase 2 Inhibitors
Disease Progression
Enzyme-Linked Immunosorbent Assay
Matrix Metalloproteinase 7
Neoplasm Metastasis
Prostaglandin-Endoperoxide Synthases
Prostate
Prostatic Neoplasms
Receptors, Prostaglandin E
RNA, Messenger
Tissue Inhibitor of Metalloproteinase-1
Cyclooxygenase 2 Inhibitors
Matrix Metalloproteinase 7
Prostaglandin-Endoperoxide Synthases
RNA, Messenger
Receptors, Prostaglandin E
Tissue Inhibitor of Metalloproteinase-1