Loss of anti-mitotic effects of Bcl-2 with retention of anti-apoptotic activity during tumor progression in a mouse model
Loss of anti-mitotic effects of Bcl-2 with retention of anti-apoptotic activity during tumor progression in a mouse model
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DOI：
10.1038/sj.onc.1203073
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发表时间：
1999-11-11
期刊：
影响因子：
8
通讯作者：
Russell, RG
中科院分区：
文献类型：
--
作者：
Furth, PA;Bar-Peled, U;Russell, RG
Bcl-2是一种抗凋亡和抗增殖的蛋白，在包括乳腺癌在内的几种不同的人类癌症中过表达，我们在WAP-TAg转基因乳腺癌进展小鼠模型上叠加了乳腺上皮细胞中Bcl-2功能的获得，以确定其在肿瘤发生的三个关键阶段对上皮细胞存活和增殖的影响：初始增殖过程、增生和癌变。在初始增殖过程中，Bcl-2强烈抑制细胞凋亡和有丝分裂活性。然而，随着肿瘤发展到增生和腺癌，对有丝分裂活性的抑制作用就消失了。相反，抗凋亡活性在增生和腺癌中持续存在。这些结果表明，Bcl-2对上皮细胞增殖和凋亡的抑制作用在肿瘤进展过程中是可以分离的。在这个模型中，抗凋亡活性的保留和抗增殖作用的丧失导致肿瘤早期出现。
Bcl-2 is an anti-apoptotic and anti-proliferative protein over-expressed in several different human cancers including breast, Gain of Bcl-2 function in mammary epithelial cells was superimposed on the WAP-TAg transgenic mouse model of breast cancer progression to determine its effect on epithelial cell survival and proliferation at three key stages in oncogenesis: the initial proliferative process, hyperplasia, and cancer. During the initial proliferative process, Bcl-2 strongly inhibited both apoptosis and mitotic activity. However as tumorigenesis progressed to hyperplasia and adenocarcinoma, the inhibitory effects on mitotic activity were lost. In contrast, anti-apoptotic activity persisted in both hyperplasias and adenocarcinomas. These results demonstrate that the inhibitory effect of Bcl-2 on epithelial cell proliferation and apoptosis can separate during cancer progression. In this model, retention of anti-apoptotic activity with loss of anti-proliferative action resulted in earlier tumor presentation.