| Budget Amount *help |
¥12,290,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2007: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Research Abstract |
This study was carried out to elucidate the role of lysophosphatidic acid (LPA) and LPA-relating molecules in the development and progression of prostate cancer. Prostate tissue samples were surgically obtained from 10 patients with localized prostate cancer and 7 patients with invasive bladder cancer. Cancer cells, high grade intraepithelial neoplasia (HGPIN), benign hyperplastic glands, normal glands, and their corresponding stromal cells were isolated by laser capture microdissection. Normal glands and its corresponding stroma from the prostate of bladder cancer patients were referred as a control. mRNA levels of three LPA receptors, LPA1, LPA2, LPA3, two LPA-synthetic enzymes, autotaxin (ATX), acylglycerol kinase (AGK), and a LPA-degradation enzyme, prostatic acid phosphatase (PAP), were quantitatively assessed. Gene expression levels were also evaluated in human prostate cancer LNCaP, PC-3, and DU-145 cells.LPA1 mRNA level was significantly decreased in HGPIN and cancer epithelia as compared to the benign glands. LPA3 mRNA level was elevated in cancer epithelia as compared to control benign glands. LPA3, AGK, and PAP gene expressions were predominant in LNCaP cells while LPA1 and ATX gene expressions were predominant in PC-3 and Du-145 cells. In BPH, elevated expression of AGK in stroma and PAP in epithelia was simultaneously found. LPA stimuli via LPA3 may play a pivotal role in the development of prostate cancer. Switching of predominant type of LPA receptors (LPA3 to LPA1) may be involved in the progression and/or androgen independence.
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