p27KIP1对恶性胶质瘤细胞中端粒酶活性的下调作用。

Down-regulation of telomerase activity in malignant glioma cells by p27KIP1.

作者信息

Kanzawa Takao, Komata Tadashi, Kyo Satoru, Germano Isabelle M, Kondo Yasuko, Kondo Seiji

机构信息

Department of Neurosurgery, Mount Sinai School of Medicine, New York, NY 10029, USA.

出版信息

Int J Oncol. 2003 Dec;23(6):1703-8.

PMID:14612944

Abstract

The cyclin-dependent kinase inhibitor p27KIP1 is considered not only a prognostic factor in cancer, but also a promising anti-cancer agent. However, the relationship between p27KIP1 and telomerase, that has potential as tumor-marker, remains to be elucidated. In this study, using the recombinant adenoviral vector expressing p27KIP1 (Adp27KIP1), we investigated whether p27KIP1 affects telomerase activity in malignant glioma U373-MG cells. Overexpression of p27KIP1 suppressed telomerase activity in tumor cells. The down-regulation of telomerase was due to inhibition of the human telomerase reverse transcriptase (hTERT) gene expression at the transcriptional level. This inhibitory effect was partially induced by interfering with binding sites of the hTERT core promoter for transcription factors Myc and Sp1. These findings identify a novel role for p27KIP1 in down-regulation of telomerase activity.

摘要

细胞周期蛋白依赖性激酶抑制剂p27KIP1不仅被认为是癌症的一个预后因素，也是一种很有前景的抗癌药物。然而，p27KIP1与具有肿瘤标志物潜力的端粒酶之间的关系仍有待阐明。在本研究中，我们使用表达p27KIP1的重组腺病毒载体（Adp27KIP1），研究了p27KIP1是否影响恶性胶质瘤U373-MG细胞中的端粒酶活性。p27KIP1的过表达抑制了肿瘤细胞中的端粒酶活性。端粒酶的下调是由于在转录水平上抑制了人端粒酶逆转录酶（hTERT）基因的表达。这种抑制作用部分是通过干扰hTERT核心启动子与转录因子Myc和Sp1的结合位点而诱导的。这些发现确定了p27KIP1在下调端粒酶活性方面的新作用。