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首页> 外文期刊>Molecular and Cellular Biology >E2F4 and E2F1 Have Similar Proliferative Properties but Different Apoptotic and Oncogenic Properties In Vivo
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E2F4 and E2F1 Have Similar Proliferative Properties but Different Apoptotic and Oncogenic Properties In Vivo

机译：E2F4和E2F1具有相似的增殖特性，但体内具有不同的凋亡和致癌特性

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Loss of retinoblastoma (Rb) tumor suppressor function, as occurs in many cancers, leads to uncontrolled proliferation, an increased propensity to undergo apoptosis, and tumorigenesis. Rb negatively regulates multiple E2F transcription factors, but the role of the different E2F family members in manifesting the cellular response to Rb inactivation is unclear. To study the effect of deregulated E2F4 activity on cell growth control and tumorigenesis, transgenic mouse lines expressing the E2F4 gene under the control of a keratin 5 (K5) promoter were developed, and their phenotypes were compared to those of previously generated K5 E2F1 transgenic mice. In contrast to what has been observed in vitro, ectopically expressed E2F4 was found to localize to the nucleus and induce proliferation to an extent similar to that induced by E2F1 in transgenic tissue. Unlike E2F1, E2F4 does not induce apoptosis, and this correlates with the differential abilities of these two E2F species to stimulatep19ARF expression in vivo. To examine the role of E2F4 in tumor development, the mouse skin two-stage carcinogenesis model was utilized. Unlike E2F1 transgenic mice, E2F4 transgenic mice developed skin tumors with a decreased latency and increased incidence compared to those characteristics in wild-type controls. These findings demonstrate that while the effects of E2F1 and E2F4 on cell proliferation in vivo are similar, their apoptotic and oncogenic properties are quite different.
机译：视网膜母细胞瘤（Rb）肿瘤抑制功能的丧失（如许多癌症中所发生的）会导致不受控制的增殖，增加的发生凋亡的倾向以及肿瘤的发生。 Rb负调控多个E2F转录因子，但尚不清楚不同的E2F家族成员在表达对Rb失活的细胞反应中的作用。为了研究E2F4活性失调对细胞生长控制和肿瘤发生的影响，开发了在角蛋白5（K5）启动子控制下表达E2F4基因的转基因小鼠品系，并将其表型与先前产生的K5 E2F1转基因小鼠进行了比较。 。与在体外观察到的相反，发现异位表达的E2F4定位于细胞核并诱导增殖，其程度与转基因组织中E2F1诱导的程度相似。与E2F1不同，E2F4不会诱导细胞凋亡，这与这两个E2F物种在体内刺激 p19 ARF 表达的能力不同有关。为了检查E2F4在肿瘤发展中的作用，使用了小鼠皮肤两阶段癌变模型。与E2F1转基因小鼠不同，与野生型对照相比，E2F4转基因小鼠发生皮肤肿瘤的潜伏期缩短，发病率增加。这些发现表明，尽管E2F1和E2F4对体内细胞增殖的影响相似，但它们的凋亡和致癌特性却大不相同。

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