Claudio P P, Howard C M, Baldi A, De Luca A, Fu Y, Condorelli G, Sun Y, Colburn N, Calabretta B, Giordano A
Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Cancer Res. 1994 Nov 1;54(21):5556-60.
The retinoblastoma tumor suppressor gene product, as well as its related protein p107, has been shown clearly to exert its growth suppressive effects in a cell cycle dependent manner. In this study we demonstrate that the introduction of our recently cloned Rb family member p130/pRb2 causes growth arrest in three tumor cell lines. In addition, in the nasopharyngeal carcinoma derived cell line HONE-1, we identified a low level of expression of p130/pRb2, possibly due to gene rearrangement, and a drastic reduction in proliferation upon introduction of a constitutive active p130/pRb2 complementary DNA clone. Furthermore, we were able to dissect distinct properties of the Rb family by demonstrating that p130/pRb2 inhibits proliferation of the glioblastoma cell line T98G, which is resistant to the growth suppressive effects of both pRb and p107. Our studies demonstrate that the Rb family proteins identified to date may complement each other but they are not fully functionally redundant.
视网膜母细胞瘤肿瘤抑制基因产物及其相关蛋白p107已被明确证明以细胞周期依赖性方式发挥其生长抑制作用。在本研究中,我们证明了我们最近克隆的Rb家族成员p130/pRb2的导入会导致三种肿瘤细胞系生长停滞。此外,在鼻咽癌衍生的细胞系HONE-1中,我们发现p130/pRb2表达水平较低,可能是由于基因重排,并且在导入组成型活性p130/pRb2互补DNA克隆后增殖急剧减少。此外,我们通过证明p130/pRb2抑制胶质母细胞瘤细胞系T98G的增殖,能够剖析Rb家族的不同特性,该细胞系对pRb和p107的生长抑制作用均具有抗性。我们的研究表明,迄今为止鉴定出的Rb家族蛋白可能相互补充,但它们在功能上并非完全冗余。