Expression of autotaxin and acylglycerol kinase in prostate cancer: association with cancer development and progression.
Lysophosphatidic acid (LPA) may enhance diverse biologic activities in prostate cancer. This study was conducted to analyze expression levels of LPA-producing enzymes, autotaxin (ATX) and acylglycerol kinase (AGK), in prostate cancer with relevance to clinicopathological parameters. Real-time RT-PCR and western blotting were performed for ATX and AGK in non-neoplastic prostate cells (PrECs and PrSCs) and prostate cancer cell-lines (DU-145, PC-3, LNCaP, and AILNCaP). Immunohistochemical analyses were conducted in tissue specimens of 132 localized prostate cancer patients who underwent radical prostatectomy between 2001 and 2007 (median observation period, 22 months). Both enzymes were negatively expressed in PrECs and PrSCs at mRNA and protein levels. ATX expression was higher than AGK in AILNCaP, DU-145, and PC-3 cell-lines, while AGK was mainly expressed in LNCaP cells. Immunohistochemically, ATX and AGK expressions were negative in non-neoplastic epithelia, while both were weakly expressed in the majority of high-grade intra-epithelial neoplasia (HG-PIN). In cancer foci, ATX and AGK expressions were strong in 49% and 62%, weak in 40% and 32%, and negative in 11% and 6%, respectively. Expressions of both enzymes were significantly correlated with primary Gleason grade of cancer foci (P < 0.0001) and capsular invasion (P = 0.03 and 0.003 respectively). ATX expression was significantly correlated with probability of prostate specific antigen (PSA)-failure after surgery (P < 0.0001). In conclusion, LPA-producing enzymes (ATX and AGK) were frequently expressed in prostate cancer cells and precancerous HG-PIN. In particular, high expression levels of ATX were associated with both malignant potentials and poor outcomes.
Nouh
Mohammed Ahmed Abdel Muneem
MA
Department of Urology, Kagawa University Faculty of Medicine, Miki-cho, Kagawa, Japan.
Wu
Xiu-Xian
XX
Okazoe
Homare
H
Tsunemori
Hiroyuki
H
Haba
Reiji
R
Abou-Zeid
Abdel Muneem Mohammed
AM
Saleem
Mohammed Diaa
MD
Inui
Masashi
M
Sugimoto
Mikio
M
Aoki
Junken
J
Kakehi
Yoshiyuki
Y
D000368:Aged; D002478:Cells, Cultured; D018450:Disease Progression; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000378:metabolism*; D043264:Phosphodiesterase I / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011379:Prognosis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011755:Pyrophosphatases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000099189:Lysophospholipase D
D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011755:Pyrophosphatases; D012333:RNA, Messenger; D000099189:Lysophospholipase D; C492429:AGK protein, human