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KLF6, a Candidate Tumor Suppressor Gene Mutated in Prostate Cancer

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Science  21 Dec 2001:
Vol. 294, Issue 5551, pp. 2563-2566
DOI: 10.1126/science.1066326

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Abstract

Kruppel-like factor 6 (KLF6) is a zinc finger transcription factor of unknown function. Here, we show that theKLF6 gene is mutated in a subset of human prostate cancer. Loss-of-heterozygosity analysis revealed that one KLF6allele is deleted in 77% (17 of 22) of primary prostate tumors. Sequence analysis of the retained KLF6 allele revealed mutations in 71% of these tumors. Functional studies confirm that whereas wild-type KLF6 up-regulates p21 (WAF1/CIP1) in a p53-independent manner and significantly reduces cell proliferation, tumor-derived KLF6 mutants do not. Our data suggest thatKLF6 is a tumor suppressor gene involved in human prostate cancer.

  • * These authors contributed equally to this work.

  • Present address: Structural Neurobiology and Proteomics Laboratory, Department of Biochemistry and Molecular Biology, FUHS/Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA.

  • To whom correspondence should be addressed. E-mail: frieds02{at}doc.mssm.edu

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