Arachidonic acid metabolism in human prostate cancer.
The arachidonic acid pathway is important in the development and progression of numerous malignant diseases, including prostate cancer. To more fully evaluate the role of individual cyclooxygenases (COXs), lipoxygenases (LOXs) and their metabolites in prostate cancer, we measured mRNA and protein levels of COXs and LOXs and their arachidonate metabolites in androgen-dependent (LNCaP) and androgen-independent (PC-3 and DU145) prostate cancer cell lines, bone metastasis-derived MDA PCa 2a and MDA PCa 2b cell lines and their corresponding xenograft models, as well as core biopsy specimens of primary prostate cancer and nonneoplastic prostate tissue taken ex vivo after prostatectomy. Relatively high levels of COX-2 mRNA and its product PGE2 were observed only in PC-3 cells and their xenografts. By contrast, levels of the exogenous 12-LOX product 12-HETE were consistently higher in MDA PCa 2b and PC-3 cells and their corresponding xenograft tissues than were those in LNCaP cells. More strikingly, the mean endogenous level of 12-HETE was significantly higher in the primary prostate cancers than in the nonneoplastic prostate tissue (0.094 vs. 0.010 ng/mg protein, respectively; p=0.019). Our results suggest that LOX metabolites such as 12-HETE are critical in prostate cancer progression and that the LOX pathway may be a target for treating and preventing prostate cancer.
Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. pyang@mdanderson.org
Peiying
P
Yang
Carrie A
CA
Cartwright
Jin
J
Li
Sijin
S
Wen
Ina N
IN
Prokhorova
Imad
I
Shureiqi
Patricia
P
Troncoso
Nora M
NM
Navone
Robert A
RA
Newman
Jeri
J
Kim
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000728:Androgens / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058945:Lipoxygenases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D012333:RNA, Messenger; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D058945:Lipoxygenases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone