KLF6，一种在前列腺癌中发生突变的候选抑癌基因。

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

作者信息

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

机构信息

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

出版信息

Science. 2001 Dec 21;294(5551):2563-6. doi: 10.1126/science.1066326.

DOI:10.1126/science.1066326

PMID:11752579

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.

摘要

Kruppel样因子6（KLF6）是一种功能未知的锌指转录因子。在此，我们表明KLF6基因在一部分人类前列腺癌中发生突变。杂合性缺失分析显示，在77%（22个中的17个）的原发性前列腺肿瘤中，一个KLF6等位基因被删除。对保留的KLF6等位基因进行序列分析发现，这些肿瘤中有71%存在突变。功能研究证实，野生型KLF6以不依赖p53的方式上调p21（WAF1/CIP1）并显著降低细胞增殖，而肿瘤来源的KLF6突变体则不然。我们的数据表明，KLF6是一种参与人类前列腺癌的肿瘤抑制基因。