The tumor-selective over-expression of the human Hsp 70 gene is attributed to the aberrant controls at both initiation and elongation levels of transcription
The tumor-selective over-expression of the human Hsp 70 gene is attributed to the aberrant controls at both initiation and elongation levels of transcription
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DOI：
10.1038/sj.cr.7290154
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发表时间：
2003-04-01
期刊：
影响因子：
44.1
通讯作者：
Zhu, D
中科院分区：
文献类型：
--
作者：
Cai, L;Zhu, D
人类Hsp70基因的肿瘤选择性过表达已在人类肿瘤中得到充分证实，其与预后不良、化疗和放射治疗难治以及特别是晚期肿瘤病变有关。然而，在肿瘤中控制Hsp70表达的畸变的性质和细节仍然是谜。通过比较不同的上游片段的Hsp70基因的每一个的能力，以驱动荧光素酶报告基因的肿瘤细胞系的上下文中不同的p53状态和不朽的正常肝细胞系，我们证明了在一个非常详细的缺陷的控制机制，在启动和延长水平的转录是有助于其表达的肿瘤选择性的配置文件。我们的数据不仅为我们理解Hsp70基因的肿瘤特异性过表达提供了新的见解，而且为合理利用以Hsp70为中心的肿瘤选择性机制来靶向人类肿瘤的治疗基因表达铺平了道路。
The tumor selective over-expression of the human Hsp70 gene has been well documented in human tumors, linked to the poor prognosis, being refractory to chemo- and radio-therapies as well as the advanced stage of tumorous lesions in particular. However, both the nature and details of aberrations in the control of the Hsp70 expression in tumor remain enigmatic. By comparing various upstream segments of the Hsp70 gene for each's ability to drive the luciferase reporter genes in the context of the tumor cell lines varying in their p53 status and an immortal normal liver cell line, we demonstrated in a great detail the defects in the control mechanisms at the both initiation and elongation levels of transcription being instrumental to the tumor selective profile of its expression. Our data should not only offer new insights into our understanding of the tumor specific over-expression of the human Hsp70 gene, but also paved the way for the rational utilization of the tumor selective mechanism with the Hsp70 at the central stage for targeting the therapeutic gene expression to human tumors.