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Cyclooxygenase‐2 promotes prostate cancer progression
Author(s) -
Fujita Hiroshi,
Koshida Kiyoshi,
Keller Evan T.,
Takahashi Yoshitake,
Yoshimito Tanihiro,
Namiki Mikio,
Mizokami Atsushi
Publication year - 2002
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10152
Subject(s) - lncap , angiogenesis , cancer research , prostate cancer , cyclooxygenase , carcinogenesis , transfection , endocrinology , biology , medicine , cancer cell , cancer , cell culture , enzyme , biochemistry , genetics
BACKGROUND Cyclooxygenase (COX) ‐2, an inducible isoform of COX, has been observed to be expressed in prostate cancer. Several studies have reported that COX‐2 overexpression is associated with carcinogenesis, cell growth, angiogenesis, apoptosis, and invasiveness in a variety of tumor types. METHODS To investigate the function of COX‐2 in prostate cancer directly, we stably transfected human full‐length COX‐2 cDNA into LNCaP cells (LNCaP‐COX‐2), which express low levels of endogenous COX‐2. RESULTS The level of COX‐2 mRNA and protein and the COX activity in COX‐2 LNCaP‐COX‐2 cells was significantly increased compared with parent and control‐transfected cells. Overexpression of COX‐2 increased both proliferation in vitro and tumor growth rate in vivo. However, the pro‐tumor effect was neither associated with changes of androgen receptor (AR) expression level nor AR activity. Furthermore, addition of the major metabolites of COX‐2–mediated arachidonic acid metabolism did not alter the proliferation of LNCaP‐COX‐2 cells in vitro. LNCaP‐COX‐2 cells had increased secretion of vascular endothelial growth factor (VEGF) protein, suggesting that angiogenesis induced by COX‐2 stimulates tumor growth in vivo. CONCLUSION These data demonstrate that COX‐2 contributes to prostate cancer progression and suggest that it mediates this effect, in part, through increased VEGF. Prostate 53: 232–240, 2002. © 2002 Wiley‐Liss, Inc.