SV40 and Notch-I: multi-functionality meets pleiotropy.
SV40 and Notch-I: multi-functionality meets pleiotropy.
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SV40 和 Notch-I：多功能性与多效性的结合。
DOI：
10.1007/978-3-540-74264-7_14
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发表时间：
2004
影响因子：
--
通讯作者：
Bocchetta,M
中科院分区：
文献类型：
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作者：
Carbone,M;Bocchetta,M
我们发现猿猴病毒40 （SV40）感染人间皮细胞可诱导Notch-1。Notch-1的上调是在转录水平上实现的，并且需要大（90-100 kDa）和小（20 kDa） SV40肿瘤抗原的活性。在组织培养中，sv40转化的间皮瘤细胞系中Notch-1表达上调，而Notch-1仅在sv40阳性间皮瘤中过表达。Notch-1的化学失活导致sv40转化的人间皮细胞生长停滞。我们的研究结果表明，Notch-1激活在sv40介导的癌变中起重要作用。Notch-1是影响细胞分化、增殖和凋亡的多效性基因。Notch-1激活的作用具有物种和细胞类型特异性，即在不同物种或同一物种内的细胞类型中，Notch-1信号可以引起相反的作用。在本章中，我们回顾了Notch信号的一些一般方面，以及Notch信号如何调节分化、细胞周期和凋亡。我们将讨论Notch与人类癌症的最新数据。然后，我们将处理关于一种特定形式的肺癌（恶性间皮瘤）的最新信息，以及SV40在这种人类癌症的发病机制中的作用。我们将详细介绍SV40介导的细胞转化，以及SV40在体外感染后与人原代间皮细胞的特异性相互作用。最后，我们将讨论最近发现的SV40介导的致癌性与Notch-1信号之间的联系，SV40感染的间皮瘤细胞和SV40间皮瘤中SV40和Notch-1之间的相互作用。我们讨论了sv40转化的人类细胞生长如何需要Notch-1诱导。最后，我们讨论了干扰Notch-1表达的策略如何导致sv40阳性转化细胞凋亡，因此可能为sv40阳性间皮瘤患者提供新的可能的治疗方法。
We have discovered that Simian virus 40 (SV40) infection of human mesothelial cells induces Notch-1. Upregulation of Notch-1 is achieved at the transcriptional level and requires the activity of both the large (90–100 kDa) and the small (20 kDa) SV40 tumor antigens. Notch-1 upregulation is maintained in SV40-transformed mesothelial cell lines in tissue culture, and Notch-1 is overexpressed only in SV40-positive mesotheliomas. Chemical inactivation of Notch-1 causes cell growth arrest of SV40-transformed human mesothelial cells. Our findings indicate that Notch-1 activation plays an important role in SV40-mediated carcinogenesis. Notch-1 is a pleiotropic gene that influences cell differentiation, proliferation and apoptosis. The effects of Notch-1 activation are species and cell type specific, in that, in different species or cell type within the same species, Notch-1 signaling can cause opposite effects. In this chapter, we review some general aspects of Notch signaling, and how Notch signaling regulates differentiation, the cell cycle and apoptosis. Recent data involving Notch and human cancer will be discussed. Then, we will deal with the current information regarding a specific form of lung cancer (malignant mesothelioma) and the involvement of SV40 in the pathogenesis of this form of human cancer. We will enter into the details of SV40-mediated cell transformation, and the specific interaction between SV40 and primary human mesothelial cells when infected with SV40 in vitro. Finally, we will discuss the recently discovered link between SV40-mediated carcinogenicity and Notch-1 signaling, the interaction between SV40 and Notch-1 in SV40 infected mesothelial cells and in SV40 mesotheliomas. We discuss how Notch-1 induction is required for the growth of SV40-transformed human cells. Finally, we discuss how strategies that interfere with Notch-1 expression may cause apoptosis of SV40-positive transformed cells, and therefore may represent new possible therapeutic approaches for SV40-positive mesothelioma patients.