Leman Eddy S, Arlotti Julie A, Dhir Rajiv, Greenberg Norman, Getzenberg Robert H
Department of Urology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pennsylvania 15232, USA.
J Cell Biochem. 2002;86(2):203-12. doi: 10.1002/jcb.10216.
The nuclear matrix (NM) contains a number of proteins that have been found to be associated with transformation. We have previously identified changes in the NM associated with prostate cancer. In this study, we examine the molecular changes that are associated with prostate cancer development in transgenic adenocarcinoma of mouse prostate (TRAMP) model by studying the differences in the NM proteins (NMPs). We collected prostates from the TRAMP males at six critical time points: 6 weeks (puberty), 11 and 19 weeks (development of mild hyperplasia), 25 weeks (development of severe hyperplasia), 31 and 37 weeks (development of neoplasia). The nuclear matrices from the prostates collected at these time points were then isolated and the NMPs were characterized by high-resolution two-dimensional gel electrophoresis. We found three NMPs (E1A, E1B, and E1C) that were present in the 6-week-old prostate and two NMPs (E2A and E2B) that were present in the 11-week-old prostate. These NMPs were absent in the 31- and 37-week-old prostate. We also found five NMPs (E3A-E3E) that were present in the 31-week-old prostate, but absent in the earlier time points. In addition, three NMPs (Le1, Le2, Le3) were present at higher expression in the 6-, 11-, 19-, and 25-weeks old TRAMP prostates, but they were expressed lower during the development of neoplasia at 31- and 37-weeks old. Identification of these NMPs permits the development of novel markers that can characterize various stages of prostate cancer development as well as potentially therapeutic targets.
核基质（NM）包含许多已被发现与细胞转化相关的蛋白质。我们之前已经确定了与前列腺癌相关的核基质变化。在本研究中，我们通过研究核基质蛋白（NMPs）的差异，来检测在小鼠前列腺转基因腺癌（TRAMP）模型中与前列腺癌发生发展相关的分子变化。我们在六个关键时间点收集TRAMP雄性小鼠的前列腺：6周（青春期）、11周和19周（轻度增生发展期）、25周（重度增生发展期）、31周和37周（肿瘤形成期）。然后分离这些时间点收集的前列腺的核基质，并通过高分辨率二维凝胶电泳对NMPs进行表征。我们发现三个NMPs（E1A、E1B和E1C）存在于6周龄的前列腺中，两个NMPs（E2A和E2B）存在于11周龄的前列腺中。这些NMPs在31周和37周龄的前列腺中不存在。我们还发现五个NMPs（E3A - E3E）存在于31周龄的前列腺中，但在早期时间点不存在。此外，三个NMPs（Le1、Le2、Le3）在6周、11周、19周和25周龄的TRAMP前列腺中高表达，但在31周和37周龄肿瘤形成期表达较低。鉴定这些NMPs有助于开发新的标志物，这些标志物可以表征前列腺癌发展过程的各个阶段以及潜在的治疗靶点。
