Russell R L, Pedersen A N, Kantor J, Geisinger K, Long R, Zbieranski N, Townsend A, Shelton B, Brünner N, Kute T E
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1072, USA.
Br J Cancer. 1998 Sep;78(6):710-7. doi: 10.1038/bjc.1998.566.
Low expression of the antimetastatic gene nm23 has been associated with shorter overall survival in breast cancer. To better understand the mechanism(s) of action of this protein, we compared the levels of the nm23 protein in 152 breast cancer samples with other factors known to be involved in metastasis or related to prognosis. There was no significant relationship between either of the nm23 isoforms and cathepsin D (Cat-D), urokinase plasminogen activator (uPA), its inhibitor (PAI-1), steroid hormone receptors or ploidy status. A marginal inverse correlation was observed between per cent S-phase and nm23-H1 expression (r = -0.193, P = 0.047) and a positive correlation was observed between uPA receptor (uPAR) and both nm23-H1 (r = 0.263, P = 0.0018) and nm23-H2 (r = 0.230, P = 0.0064). The nm23-H1 gene was transfected into MDA-MB-231 human breast cancer cells and 12 clones were selected, of which two were characterized extensively. We found no significant differences in Cat-D, uPA, PAI-1 or uPAR, as a function of nm23 expression in either the MDA-MB-231 cells or the transfected clones. Compared with the parent cell line, we did observe a dose-dependent decrease in growth factor-stimulated motility and a decrease in metastatic potential in two clones with four- and eightfold elevated nm23-H1 expression, whereas the proliferative activities were similar. We conclude that the decreased metastatic potential might be related to down-regulation of growth factor-stimulated motility.
抗转移基因nm23的低表达与乳腺癌患者较短的总生存期相关。为了更好地理解该蛋白的作用机制，我们比较了152例乳腺癌样本中nm23蛋白的水平与其他已知参与转移或与预后相关的因素。nm23的两种同工型与组织蛋白酶D（Cat-D）、尿激酶型纤溶酶原激活剂（uPA）、其抑制剂（PAI-1）、类固醇激素受体或倍体状态之间均无显著相关性。观察到S期百分比与nm23-H1表达之间存在微弱的负相关（r = -0.193，P = 0.047），并且uPA受体（uPAR）与nm23-H1（r = 0.263，P = 0.0018）和nm23-H2（r = 0.230，P = 0.0064）之间均存在正相关。将nm23-H1基因转染到MDA-MB-231人乳腺癌细胞中，并筛选出12个克隆，其中两个进行了详细表征。我们发现，无论是在MDA-MB-231细胞还是转染的克隆中，Cat-D、uPA、PAI-1或uPAR的表达水平与nm23的表达均无显著差异。与亲代细胞系相比，我们确实观察到在两个nm23-H1表达分别升高4倍和8倍的克隆中，生长因子刺激的运动能力呈剂量依赖性降低，转移潜能也降低，而增殖活性相似。我们得出结论，转移潜能的降低可能与生长因子刺激的运动能力下调有关。
