title: Expression of autotaxin and acylglycerol kinase in prostate cancer: association with cancer development and progression.
abstract: 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.
authors: Department of Urology, Kagawa University Faculty of Medicine, Miki-cho, Kagawa, Japan.
authors: Mohammed Ahmed Abdel Muneem
authors: MA
authors: Nouh
authors: Xiu-Xian
authors: XX
authors: Wu
authors: Homare
authors: H
authors: Okazoe
authors: Hiroyuki
authors: H
authors: Tsunemori
authors: Reiji
authors: R
authors: Haba
authors: Abdel Muneem Mohammed
authors: AM
authors: Abou-Zeid
authors: Mohammed Diaa
authors: MD
authors: Saleem
authors: Masashi
authors: M
authors: Inui
authors: Mikio
authors: M
authors: Sugimoto
authors: Junken
authors: J
authors: Aoki
authors: Yoshiyuki
authors: Y
authors: Kakehi
mesh_terms: 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
chemical_list: 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