Suppression of glioblastoma tumorigenicity by the Kruppel-like transcription factor KLF6.
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.
Kimmelman
Alec C
AC
The Derald H Ruttenberg Cancer Center, The Mount Sinai School of Medicine, New York, NY 10029, USA.
Qiao
Rui F
RF
Narla
Goutham
G
Banno
Asoka
A
Lau
Nelson
N
Bos
Paula D
PD
Nuñez Rodriguez
Nelson
N
Liang
Bertrand C
BC
Guha
Abhijit
A
Martignetti
John A
JA
Friedman
Scott L
SL
Chan
Andrew M
AM
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001932:Brain Neoplasms; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D011518:Proto-Oncogene Proteins; D051381:Rats; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C105465:KLF6 protein, human; C491358:Klf6 protein, mouse; C491357:Klf6 protein, rat; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors