Cyclin D1 overexpression and p53 inactivation immortalize primary oral keratinocytes by a telomerase-independent mechanism
Cyclin D1 overexpression and p53 inactivation immortalize primary oral keratinocytes by a telomerase-independent mechanism
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DOI：
10.1172/jci11909
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发表时间：
2001-09-01
影响因子：
15.9
通讯作者：
Rustgi, AK
中科院分区：
文献类型：
--
作者：
Opitz, OG;Suliman, Y;Rustgi, AK
人类细胞的永生化是多步骤致癌过程中的关键步骤。口腔食管癌是研究鳞状细胞癌发生的分子机制的模型系统，经常涉及细胞周期蛋白D1的过度表达和p53肿瘤抑制因子的失活。因此，我们的目标是建立细胞周期蛋白D I过表达和p53失活的原代人口腔鳞状上皮细胞（角质形成细胞）永生化的功能作用，作为向恶性转化的重要一步。细胞周期蛋白DI过表达单独诱导正常口腔角质形成细胞的复制寿命延长，而细胞周期蛋白DI过表达和p53失活的组合导致其永生化。这项研究还表明，口腔角质形成细胞的永生化可以独立于端粒酶激活，涉及端粒维持（ALT）的替代途径。
The immortalization of human cells is a critical step in multistep carcinogenesis. Oral-esophageal carcinomas, a model system to investigate molecular mechanisms underlying squamous carcinogenesis, frequently involve cyclin D1 overexpression and inactivation of the p53 tumor suppressor. Therefore, our goal was to establish the functional role of cyclin D I overexpression and p53 inactivation in the immortalization of primary human oral squamous epithelial cells (keratinocytes) as an important step toward malignant transformation. Cyclin D I overexpression alone was found to induce extension of the replicative life span of normal oral keratinocytes, whereas the combination of cyclin DI overexpression and p53 inactivation led to their immortalization. This study also demonstrates that immortalization of oral keratinocytes can be independent of telomerase activation, involving an alternative pathway of telomere maintenance (ALT).