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Suppression of glioblastoma tumorigenicity by the Kruppel-like transcription factor KLF6

Oncogene volume 23, pages 5077–5083 (2004)Cite this article

Abstract

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.

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Acknowledgements

This work was supported by NIH Grants CA78509 (AMC), and DK37340, DOD PC020770 (SLF). ACK was supported by an NCI predoctoral training Grant (CA78207). AMC is a recipient of a Career Scientist Award from the Irma T Hirschl Foundation. SB and GN were supported by Howard Hughes Medical Institute Medical Student Research Fellowships.

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Authors and Affiliations

  1. The Derald H Ruttenberg Cancer Center, The Mount Sinai School of Medicine, New York, 10029, NY, USA

    Alec C Kimmelman, Rui F Qiao, Asoka Banno, Paula D Bos, Nelson Nuñez Rodriguez, John A Martignetti & Andrew M Chan

  2. Division of Liver Diseases, Department of Medicine, The Mount Sinai School of Medicine, New York, 10029, NY, USA

    Goutham Narla & Scott L Friedman

  3. Division of Neurosurgery, Toronto Western Hospital, 399 Bathurst Street, Toronto, M5T 2S8, Ontario, Canada

    Nelson Lau & Abhijit Guha

  4. Biogen Idec, 10996 Torreyana Road, San Diego, 92121, CA, USA

    Bertrand C Liang

  5. Department of Human Genetics, The Mount Sinai School of Medicine, New York, 10029, NY, USA

    John A Martignetti

  6. Department of Pediatrics, The Mount Sinai School of Medicine, New York, 10029, NY, USA

    John A Martignetti

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  1. Alec C Kimmelman
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  2. Rui F Qiao
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Correspondence to Andrew M Chan.

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Kimmelman, A., Qiao, R., Narla, G. et al. Suppression of glioblastoma tumorigenicity by the Kruppel-like transcription factor KLF6. Oncogene 23, 5077–5083 (2004). https://doi.org/10.1038/sj.onc.1207662

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