KLF6, a candidate tumor suppressor gene mutated in prostate cancer.

KLF6, a candidate tumor suppressor gene mutated in prostate cancer.

Science (New York, N.Y.) (2001-12-26)

G Narla, K E Heath, H L Reeves, D Li, L E Giono, A C Kimmelman, M J Glucksman, J Narla, F J Eng, A M Chan, A C Ferrari, J A Martignetti, S L Friedman

PMID11752579

摘要

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.