Kimmelman Alec C, Qiao Rui F, Narla Goutham, Banno Asoka, Lau Nelson, Bos Paula D, Nuñez Rodriguez Nelson, Liang Bertrand C, Guha Abhijit, Martignetti John A, Friedman Scott L, Chan Andrew M
The Derald H Ruttenberg Cancer Center, The Mount Sinai School of Medicine, New York, NY 10029, USA.
Oncogene. 2004 Jun 24;23(29):5077-83. doi: 10.1038/sj.onc.1207662.
The Kruppel-like transcription factor KLF6 is a novel tumor-suppressor gene mutated in a significant fraction of human prostate cancer. It is localized to human chromosome 10p14-15, a region that displays frequent loss of heterozygosity in glioblastoma multiforme (GBM). Indeed, mutations of the KLF6 gene have recently been reported in this tumor type. In this study, we report that the expression of KLF6 is attenuated in human GBM when compared with primary astrocytes. Expression of KLF6 in GBM cells reverts their tumorigenicity both in vitro and in vivo, which is correlated with its transactivation of the p21/CIP1/WAF1 promoter. Additionally, KLF6 inhibits cellular transformation induced by several oncogenes (c-sis/PDGF-B, v-src, H-Ras, and EGFR) that are components of signaling cascades implicated in GBM. Our results provide the first evidence of functional tumor suppression by KFL6, and its loss may contribute to glial tumor progression.
Kruppel样转录因子KLF6是一种新的肿瘤抑制基因，在相当一部分人类前列腺癌中发生突变。它定位于人类染色体10p14 - 15，该区域在多形性胶质母细胞瘤（GBM）中经常出现杂合性缺失。事实上，最近已报道在这种肿瘤类型中存在KLF6基因的突变。在本研究中，我们报告与原代星形胶质细胞相比，KLF6在人类GBM中的表达减弱。GBM细胞中KLF6的表达在体外和体内均使其致瘤性逆转，这与其对p21/CIP1/WAF1启动子的反式激活相关。此外，KLF6抑制由几种癌基因（c-sis/PDGF-B、v-src、H-Ras和EGFR）诱导的细胞转化，这些癌基因是GBM中涉及的信号级联的组成部分。我们的结果提供了KFL6功能性肿瘤抑制的首个证据，其缺失可能导致胶质肿瘤进展。
