Gene expression Profiles of Lysophosphatidic Acid-Related Molecules in the Prostate: Relevance to Prostate Cancer and Benign Hyperplasia

Gene expression Profiles of Lysophosphatidic Acid-Related Molecules in the Prostate: Relevance to Prostate Cancer and Benign Hyperplasia
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DOI:
10.1002/pros.20879
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发表时间:
2009-02-15
期刊:
影响因子:
2.8
通讯作者:
Wu, Xiu-Xian
Wu, Xiu-Xian
中科院分区:
医学3区
文献类型:
--
作者:
Zeng, Yu;Kakehi, Yoshiyuki;Wu, Xiu-Xian

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客观的。阐明癌症、癌前病变和前列腺良性增生中溶血磷脂酸 (LPA) 相关分子的基因表达谱。材料和方法。通过手术从 10 名局限性前列腺癌患者和 7 名浸润性膀胱癌患者中获取前列腺组织样本。通过激光捕获显微切割分离来自正常前列腺、高级上皮内瘤变(HGPIN)、良性增生腺体的癌细胞和相应的基质细胞。定量评估了三种 LPA 受体 LPA1、LPA2、LPA3、两种 LPA 合成酶、自分泌运动因子 (ATX)、酰基甘油激酶 (AGK) 和一种 LPA 降解酶、前列腺酸性磷酸酶 (PAP) 的 mRNA 水平。还在三种人前列腺癌细胞系 LNCaP、PC-3 和 DU-145 中测定了相同基因的表达水平。结果。与良性腺体相比,HGPIN 和癌上皮细胞中的 LPA1 mRNA 水平显着降低。与良性腺体相比,癌上皮细胞中的 LPA3 mRNA 水平升高。 LPA3、AGK 和 PAP 主要在 LNCaP 细胞中表达,而 LPA1 和 ATX 基因在 PC-3 和 Du-145 细胞中表达。在 BPH 中,AGK 在基质中大量表达,而 PAP 在上皮细胞中占主导地位。结论。通过 LPA3 发挥作用,LPA 可能在前列腺癌的发展中发挥重要作用。 LPA 受体表达从 LPA3 转换为 LPA1,可能与前列腺癌进展和/或雄激素依赖性有关。 LPA 也可能在良性前列腺增生的发展中发挥关键作用。前列腺 69:283-292,2009。 (C) 2008 年威利利斯。公司
OBJECTIVE. To elucidate gene expression profiles of lysophosphatidic acid (LPA)-related molecules in cancer, pre-cancerous lesion, and benign hyperplasia of the prostate.MATERIALS AND METHODS. Prostate tissue samples were surgically obtained from 10 patients with localized prostate cancer and seven patients with invasive bladder cancer. Cancer cells and the corresponding stromal cells from normal prostate, high grade intraepithelial neoplasia (HGPIN), benign hyperplastic glands were isolated by laser capture microdissection. mRNA levels of three LPA receptors, LPA1, LPA2, LPA3, two LPA-synthesizing enzymes, autotaxin (ATX), acylglycerol kinase (AGK), and a LPA-degradation enzyme, prostatic acid phosphatase (PAP), were quantitatively assessed. The expression levels of the same genes were also determined in three human prostate cancer cell lines LNCaP, PC-3, and DU-145.RESULTS. LPA1 mRNA level was significantly decreased in HGPIN and cancer epithelia when compared to the benign glands. LPA3 mRNA level was elevated in cancer epithelia compared to benign glands. LPA3, AGK, and PAP were predominantly expressed in LNCaP cells while LPA1 and ATX gene expressions were found in PC-3 and Du-145 cells. In BPH, AGK was abundantly expressed in the stroma while PAP was predominant in epithelial cells.CONCLUSIONS. By acting via LPA3, LPA may play an important role in the development of prostate cancer. Switching of LPA receptor expression from LPA3 to LPA1, may be involved in prostate cancer progression and/or androgen independence. LPA may also play a key role in the development of benign prostatic hyperplasia. Prostate 69:283-292,2009. (C) 2008 Wiley-Liss. Inc.