Causal relationship between the loss of RUNX3 expression and gastric cancer

被引：1110

作者：

Li, QL

Ito, K

Sakakura, C

Fukamachi, H

Inoue, K

Chi, XZ

Lee, KY

Nomura, S

Lee, CW

Han, SB

Kim, HM

Kim, WJ

Yamamoto, H

Yamashita, N

Yano, T

Ikeda, T

Itohara, S

Inazawa, J

Abe, T

Hagiwara, A

Yamagishi, H

Ooe, A

Kaneda, A

Sugimura, T

Ushijima, T

Bae, SC ^{[1
]}

Ito, Y

机构：

[1] Chungbuk Natl Univ, Coll Med, Dept Biochem, Inst Med Res, Cheongju 361763, South Korea

[2] Kyoto Univ, Inst Virus Res, Dept Viral Oncol, Sakyo Ku, Kyoto 6068507, Japan

[3] Kyoto Prefectural Univ Med, Dept Digest Surg, Kamigyo Ku, Kyoto 6020841, Japan

[4] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, Tokyo 1130033, Japan

[5] Osaka Univ, Grad Sch Med, Dept Pathol, Suita, Osaka 5650871, Japan

[6] Korea Res Inst Biosci & Biotechnol, Taejon 305600, South Korea

[7] Chungbuk Natl Univ, Coll Med, Dept Urol, Cheongju 361763, South Korea

[8] Kyoto Univ, Inst Virus Res, Lab Adv Biol Informat, Sakyo Ku, Kyoto 6068507, Japan

[9] Natl Canc Ctr, Res Inst, Chuo Ku, Tokyo 1040045, Japan

[10] Tokyo Med & Dent Univ, Med Res Inst, Bunkyo Ku, Tokyo 1138510, Japan

来源：

CELL | 2002年 / 109卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

D O I：

10.1016/S0092-8674(02)00690-6

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：

Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells. Between 45% and 60% of human gastric cancer cells do not significantly express RUNX3 due to hemizygous deletion and hypermethylation of the RUNX3 promoter region. Tumorigenicity of human gastric cancer cell lines in nude mice was inversely related to their level of RUNX3 expression, and a mutation (R122C) occurring within the conserved Runt domain abolished the tumor-suppressive effect of RUNX3, suggesting that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer.

引用

页码：113 / 124

页数：12

共 44 条

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