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

为了研究人类前列腺癌的分子异常，用限制性地标基因组扫描(RLGS)方法检测了3种前列腺癌细胞系LNCaP、PC-3和DU-145的基因组DNA，RLGS方法是一种二维凝胶分析，可以评估大约2000个NOT I标志。在LNCaP、PC-3和DU-145 DNA中分别检测到24、18和23个扩增斑点。3种细胞系均有11个斑点增强，扩增范围为正常的2.1~134.1倍。本文研究了6例异质性前列腺癌的基因组DNA的变化，以及肿瘤内单个和组织学上不同的病灶。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35个点发生了变化。尽管肿瘤的组织学分级不同，但与对照组相比，所有肿瘤样本中的3个共同点显示出一致的强度放大，而其他8个共同点的强度显示出一致的降低。此外，从单个肿瘤中分离出来的组织学上相同的病灶之间也发生斑点改变。在RLGS产生的DNA图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异常，同时也表明前列腺癌不仅在组织上是异质性的和多灶性的，而且在基因上也是多中心的。相反，在所检查的16例前列腺增生症中，每一例中都有2-10个斑点与正常前列腺的相应斑点相比发生了变化，但几乎没有发现任何增生样本的共同斑点图谱。在某些形式的人类良性前列腺增生症的发病机制中，可能没有一致的基因变化。这些结果表明，人类前列腺癌可能会出现常见的基因异常。

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.