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Genetic analysis in human prostate carcinoma detected by two-dimensinal gel electrophoresis (RLGS method)

二维凝胶电泳（RLGS法）检测人前列腺癌的基因分析

基本信息

批准号：
08670210
负责人：
KONISHI Noboru
金额：
$ 1.54万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670210/
关键词：
prostate carcinoma RLGS genome heterogeneity being prostatic hyperplasia cell lines

项目摘要

To explore the molecular abnormalities in human prostate carcinome, the genomic DNAs extracted from 3 prostate cell lines-LNCaP,PC-3 and DU-145-were examined using restriction landmark genomic scanning (RLGS) methodology, a 2-dimensional gel analysis which allows evaluation of approximately, 2,000 Not I landmarks. The 24,18 and 23 amplified spots were detected in LNCaP,PC-3 and DU-145 DNA,respectively. Eleven spots were commonly intensified in all 3 cell lines, with a range of amplification of 2.1 to 134.1-fold over normal. Alterations in the genomic DNAs of 6 heterogeneous prostate carcinomas, as well as that of indiviual and histologically distinct foci within the tumors, were examined. In this study, comparison of cancer DNAs against normal prostate DNA controls yielded alterations in at least 35 spots. Despite differences in the histological grading of tumors, 3 spots common to all tumor samples showed consistent amplification of intensity and 8 other common spots demonstrated consistent reduction of intensity when compared to control. In addition, spot alterations occurred between histologically identical foci isolated from within single tumors. It is suggested that these spot changes detected in RLGS-generated DNA profiles reflect aberrations in as yet unidentified oncogenes and tumor suppressor genes, and indicate, as well, that prostate cancer is not only histologically heterogeneous and multifocal but also genetically multicentric.On the contrary, within each of the 16 hyperplasias examined, 2 to 10 spots were found with altered intensities, as compared to equivalent spots from normal prostate, but could detect few common spot profiles for any hyperplasia samples. There may be no consistent genetic changes in the pathogenesis of some forms of human benign prostatic hyperplasia. These results suggest that common genetic abnormalities may occur in carcinomas of the human prostate.

为了探索人类前列腺癌的分子异常，我们使用限制性标记基因组扫描（RLGS）方法检测了从3种前列腺细胞系lncap、PC-3和du -145中提取的基因组dna，这是一种二维凝胶分析，可以评估大约2000个Not I标记。LNCaP、PC-3和DU-145 DNA中分别检测到24、18和23个扩增点。3株细胞系均有11个斑点共同增强，扩增范围为正常的2.1 ~ 134.1倍。研究了6种异质性前列腺癌的基因组dna变化，以及肿瘤内个体和组织学上不同的病灶的基因组dna变化。在这项研究中，将癌症DNA与正常前列腺DNA对照进行比较，发现至少有35个位点发生了变化。尽管肿瘤的组织学分级存在差异，但与对照组相比，所有肿瘤样本共有的3个斑点表现出一致的强度放大，其他8个共同斑点表现出一致的强度降低。此外，从单个肿瘤中分离出来的组织学相同的病灶之间也会发生斑点改变。我们认为，在rlgs生成的DNA谱中检测到的这些斑点变化反映了尚未确定的癌基因和肿瘤抑制基因的畸变，并表明前列腺癌不仅在组织学上具有异质性和多灶性，而且在遗传上也是多中心的。相反，在检查的16个增生中，与正常前列腺的相同斑点相比，发现2至10个斑点的强度发生了变化，但在任何增生样本中都无法检测到常见的斑点特征。在某些形式的人类良性前列腺增生的发病机制中可能没有一致的遗传变化。这些结果表明，常见的遗传异常可能发生在人类前列腺癌中。