KLF6, a candidate tumor suppressor gene mutated in prostate cancer.
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.
Narla
G
G
Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 1170F, Box 1123, New York, NY, 10029, USA.
Heath
K E
KE
Reeves
H L
HL
Li
D
D
Giono
L E
LE
Kimmelman
A C
AC
Glucksman
M J
MJ
Narla
J
J
Eng
F J
FJ
Chan
A M
AM
Ferrari
A C
AC
Martignetti
J A
JA
Friedman
S L
SL
D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D018740:Genetic Heterogeneity; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats; D009154:Mutation; D020125:Mutation, Missense; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D016335:Zinc Fingers
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C105465:KLF6 protein, human; C491358:Klf6 protein, mouse; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators