KLF6 , a Candidate Tumor Suppressor Gene Mutated in Prostate Cancer-Reference-Cited by-同舟云学术

KLF6 , a Candidate Tumor Suppressor Gene Mutated in Prostate Cancer

Published:2001-12-21 Issue:5551 Volume:294 Page:2563-2566
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Narla Goutham¹,Heath Karen E.²,Reeves Helen L.¹,Li Dan¹,Giono Luciana E.¹,Kimmelman Alec C.³,Glucksman Marc J.⁴,Narla Jyothsna⁵,Eng Francis J.¹,Chan Andrew M.³,Ferrari Anna C.³⁶,Martignetti John A.²³⁷,Friedman Scott L.¹

Affiliation:

1. Division of Liver Diseases, Department of Medicine,

2. Department of Human Genetics,

3. The Derald H. Ruttenberg Cancer Center,

4. Department of Neurobiology,

5. Regional Medical Center, 225 North Jackson, San Jose, CA, 95116, USA.

6. Division of Medical Oncology, Department of Medicine, and

7. Department of Pediatrics, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 1170F, Box 1123, New York, NY, 10029, USA.

Abstract

Kruppel-like factor 6 ( KLF6 ) is a zinc finger transcription factor of unknown function. Here, we show that the KLF6 gene is mutated in a subset of human prostate cancer. Loss-of-heterozygosity analysis revealed that one KLF6 allele 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 that KLF6 is a tumor suppressor gene involved in human prostate cancer.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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