Down-regulation of drs mRNA in human prostate carcinomas

Down-regulation of drs mRNA in human prostate carcinomas
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DOI:
10.1016/s0046-8177(03)00240-5
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发表时间:
2003-07-01
期刊:
影响因子:
3.3
通讯作者:
Inoue, H
Inoue, H
中科院分区:
医学3区
文献类型:
--
作者:
Kim, CJ;Shimakage, M;Inoue, H

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我们之前报道过,drs基因具有抑制大鼠细胞fine F2808中v-src和v-K-ras转化的能力。我们还发现,drs mRNA 的表达在多种人类癌细胞系中显着降低,表明 drs mRNA 的下调与人类癌症的发展相关。为了阐明 drs 基因在前列腺癌发生中的作用,我们通过原位杂交检测了 3 个正常前列腺、13 个前列腺癌、5 个良性前列腺增生 (BPH) 和 2 个前列腺上皮内瘤变 (PIN) 组织标本中 drs 基因的表达,并通过 Northern 印迹分析检测了 3 个前列腺癌细胞系(PC3、LNCaP 和 DU145)和 2 个 BPH 组织中 drs 基因的表达。此外,通过Southern印迹分析来分析drs基因的缺失和重排。 drs mRNA在正常前列腺和BPH组织中显着表达,而在前列腺癌组织和前列腺癌细胞系中显着下调。在 PIN 的 2 个组织中,drs mRNA 呈弱表达。前列腺癌细胞系和 BPH 组织在 Southern 印迹分析的条带模式方面没有差异。这些结果表明drs mRNA的下调与前列腺癌的发展密切相关,表明drs基因在这种癌症中具有肿瘤抑制功能。 (C) 2003 Elsevier Inc. 保留所有权利。
We have previously reported that the drs gene has the ability to suppress transformation by v-src and v-K-ras in the rat cell fine F2808. We have also shown that the expression of drs mRNA is markedly reduced in a variety of human cancer cell lines, suggesting that down-regulation of drs mRNA is correlated with the development of human cancers. To clarify the role of the drs gene in prostate carcinogenesis, we examined the expression of the drs gene in 3 normal prostate, 13 prostate carcinoma, 5 benign prostate hyperplasia (BPH), and 2 prostatic intraepithelial neoplasia (PIN) tissue specimens by in situ hybridization and in 3 prostate carcinoma cell lines (PC3, LNCaP, and DU145) and 2 BPH tissues by Northern blot analysis. Furthermore, the deletion, and rearrangement of the drs gene were analyzed by Southern blot analysis. The drs mRNA was significantly expressed in normal prostate and BPH tissues, whereas it was markedly down-regulated in prostate carcinoma tissues and prostate carcinoma cell lines. In 2 tissues from PIN, drs mRNA was weakly expressed. There were no differences between prostate carcinoma cell lines and BPH tissues in terms of their banding patterns of Southern blot analysis. These results indicate that down-regulation of drs mRNA is closely correlated with development of prostate carcinoma, suggesting a tumor-suppressor function of the drs gene in this cancer. (C) 2003 Elsevier Inc. All rights reserved.