Publication Date:
2001-12-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Narla, G -- Heath, K E -- Reeves, H L -- Li, D -- Giono, L E -- Kimmelman, A C -- Glucksman, M J -- Narla, J -- Eng, F J -- Chan, A M -- Ferrari, A C -- Martignetti, J A -- Friedman, S L -- 5 P30 HD28822/HD/NICHD NIH HHS/ -- CA78207/CA/NCI NIH HHS/ -- CA79918/CA/NCI NIH HHS/ -- DK37340/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 21;294(5551):2563-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 1170F, Box 1123, New York, NY, 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11752579" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Amino Acid Substitution
;
Animals
;
Cell Division
;
Cell Line
;
Chromosome Mapping
;
Chromosomes, Human, Pair 10/genetics
;
Cyclin-Dependent Kinase Inhibitor p21
;
Cyclins/genetics/metabolism
;
*Genes, Tumor Suppressor
;
Genetic Heterogeneity
;
Humans
;
Kruppel-Like Transcription Factors
;
Loss of Heterozygosity
;
Male
;
Mice
;
Microsatellite Repeats
;
*Mutation
;
Mutation, Missense
;
Proliferating Cell Nuclear Antigen/metabolism
;
Promoter Regions, Genetic
;
Prostatic Neoplasms/*genetics
;
*Proto-Oncogene Proteins
;
Trans-Activators/chemistry/*genetics/physiology
;
Transcriptional Activation
;
Tumor Cells, Cultured
;
Up-Regulation
;
Zinc Fingers
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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