NF-κB activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer

被引:170
作者
Chen, CD [1 ]
Sawyers, CL [1 ]
机构
[1] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA
关键词
D O I
10.1128/MCB.22.8.2862-2870.2002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The transcription factor NF-kappaB regulates gene expression involved in cell growth and survival and has been implicated in progression of hormone-independent breast cancer. By expressing a dominant-active form of mitogen-activated protein kinase kinase kinase 1, by exposure to tumor necrosis factor alpha, or by overexpression of p50/p65, we show that NF-kappaB activates a transcription regulatory element of the prostate-specific antigen (PSA)-encoding gene, a marker for prostate cancer development, treatment, and progression. By DNase I footprinting, we identified four NF-kappaB binding sites in the PSA core enhancer. We also demonstrate that androgen-independent prostate cancer xenografts have higher constitutive NF-kappaB binding activity than their androgen-dependent counterparts. These results suggest a role of NF-kappaB in prostate cancer progression.
引用
收藏
页码:2862 / 2870
页数:9
相关论文
共 42 条
[1]   Transcription activating and repressing functions of the androgen receptor are differentially influenced by mutations in the deoxyribonucleic acid-binding domain [J].
Aarnisalo, P ;
Santti, H ;
Poukka, H ;
Palvimo, JJ ;
Jänne, OA .
ENDOCRINOLOGY, 1999, 140 (07) :3097-3105
[2]  
Abreu-Martin MT, 1999, MOL CELL BIOL, V19, P5143
[3]   The transcription factor NF-κB and human disease [J].
Baldwin, AS .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (01) :3-6
[4]   EMBRYONIC LETHALITY AND LIVER DEGENERATION IN MICE LACKING THE RELA COMPONENT OF NF-KAPPA-B [J].
BEG, AA ;
SHA, WC ;
BRONSON, RT ;
GHOSH, S ;
BALTIMORE, D .
NATURE, 1995, 376 (6536) :167-170
[5]   TNF-α and 9-cis-retinoic acid synergistically induce ICAM-1 expression:: Evidence for interaction of retinoid receptors with NF-KB [J].
Chadwick, CC ;
Shaw, LJ ;
Winneker, RC .
EXPERIMENTAL CELL RESEARCH, 1998, 239 (02) :423-429
[6]  
Chen MW, 1999, MOL UROL, V3, P5
[7]   A 6-kb promoter fragment mimics in transgenic mice the prostate-specific and androgen-regulated expression of the endogenous prostate-specific antigen gene in humans [J].
Cleutjens, KBJM ;
vanderKorput, HAGM ;
EhrenvanEekelen, CC ;
Sikes, RA ;
Fasciana, C ;
Chung, LW ;
Trapman, J .
MOLECULAR ENDOCRINOLOGY, 1997, 11 (09) :1256-1265
[8]  
Craft N, 1999, CANCER RES, V59, P5030
[9]   A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase [J].
Craft, N ;
Shostak, Y ;
Carey, M ;
Sawyers, CL .
NATURE MEDICINE, 1999, 5 (03) :280-285
[10]   Genistein inhibits NF-κB activation in prostate cancer cells [J].
Davis, JN ;
Kucuk, O ;
Sarkar, FH .
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 1999, 35 (02) :167-174