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


CONCLUSIONS
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.
Jia
Rui-Peng
RP
Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China.
Xu
Lu-Wei
LW
Su
Qi
Q
Zhao
Jian-Hua
JH
Li
Wen-Cheng
WC
Wang
Feng
F
Xu
Zheng
Z
D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000378:metabolism*; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000728:Androgens; D016895:Culture Media, Serum-Free; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases