Cyclooxygenase-2 expression is dependent upon epidermal growth factor receptor expression or activation in androgen independent prostate cancer

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Abstract:

Abstract

Aim: To investigate the expression of cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) and the possible mechanism in the development in androgen independent prostate cancer (AIPC). Methods: Immunohis-tochemistry was performed on paraffin-embedded sections with goat polyclonal against COX-2 and mouse monoclonal antibody against EGFR in 30 AIPC and 18 androgen dependent prostate cancer (ADPC) specimens. The effect of epidermal growth factor (EGF) treatments on the expression of COX-2 and signal pathway in PC-3 and DU-145 cells was studied using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. ELISA was used to measure prostaglandin E2 (PGE2) levels in the media of PC-3 and DU-145 incubated with EGF for 24 h. Results: COX-2 was positively expressed in AIPC and ADPC, which were predominantly in endochylema of prostate cancer (PCa) cells. Intense staining was seen in AIPC (80%) and in ADPC (55.5%), but there was no significant association between the two groups. EGFR expression was also positive in the two groups (61.8% in ADPC and 90% in AIPC, P < 0.01). A significant association was found between EGFR expression and a higher Gleason score (P < 0.05) or tumor stage (P < 0.05). The expression of PGE2 was increased in PC-3 and DU-145 cells after being incubated with EGF. Both p38MAPK and PI-3K pathway were involved in the PC-3 cell COX-2 upregulation course. In DU-145, only p38MAPK pathway was associated with COX-2 upregulation. Conclusion: EGFR activation induces COX-2 expression through PI-3K and/or p38MAPK pathways. COX-2 and EGFR inhibitors might have a cooperative anti-tumor effect in PCa.

Keywords: cyclooxygenase 2; epidermal growth factor receptor; prostatic neoplasms

Document Type: Original Article

DOI: http://dx.doi.org/10.1111/j.1745-7262.2008.00423.x

Affiliations: 1: Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China 2: Department of Pathology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China 3: Center Laboratory, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China

Publication date: September 1, 2008

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