Rodriguez-Puebla M L, LaCava M, Gimenez-Conti I B, Johnson D G, Conti C J
The University of Texas MD Anderson Cancer Center, Science Park-Research Division, Smithville 78957, USA.
Oncogene. 1998 Oct 29;17(17):2251-8. doi: 10.1038/sj.onc.1202131.
It is now evident that several genes encoding regulatory activities that control the mammalian cell cycle, particularly some that control the progression of quiescent cells through G1 and into S phase, are targets for alterations that underlie the development of neoplasms. Here, we made a sequential study of alterations in cell cycle protein expression and complex formation among cyclin, cyclin dependent kinases (CDKs) and CDK inhibitors (CKIs) during premalignant progression in SENCAR mouse skin tumors. Changes in the level of expression were observed in positive (cyclin D1, D2, and E2F family members) and negative regulators (p16Ink4a, p57Kip2) of the cell cycle. Also, we observed the formation of cyclin/CDK/CKI complexes. The amounts of these proteins and complexes increased substantially at specific times during promotion but not during malignant conversion to carcinomas. These data show that deregulation of growth control occurs in benign tumors and that subsequent mutations not involved cell-cycle regulation are probably necessary to induce invasive behavior.
现在很明显，几个编码调控活性的基因是肿瘤发生的潜在改变靶点，这些调控活性控制着哺乳动物细胞周期，特别是一些控制静止细胞从G1期进入S期进程的基因。在此，我们对SENCAR小鼠皮肤肿瘤恶变前进程中细胞周期蛋白表达以及细胞周期蛋白、细胞周期蛋白依赖性激酶（CDK）和CDK抑制剂（CKI）之间复合物形成的改变进行了序贯研究。在细胞周期的正调控因子（细胞周期蛋白D1、D2和E2F家族成员）和负调控因子（p16Ink4a、p57Kip2）中观察到表达水平的变化。此外，我们还观察到细胞周期蛋白/CDK/CKI复合物的形成。这些蛋白质和复合物的量在促癌过程中的特定时间大幅增加，但在恶性转化为癌的过程中没有增加。这些数据表明，生长控制失调发生在良性肿瘤中，随后可能需要不涉及细胞周期调控的突变来诱导侵袭行为。
