骨形态发生蛋白-2 和 -4 在人弥漫型胃癌中发挥肿瘤抑制作用。
Bone morphogenetic protein-2 and -4 play tumor suppressive roles in human diffuse-type gastric carcinoma.
机构信息
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
出版信息
Am J Pathol. 2011 Dec;179(6):2920-30. doi: 10.1016/j.ajpath.2011.08.022. Epub 2011 Oct 11.
Abstract
A relationship exists between defects in bone morphogenetic protein (BMP) signaling and formation of hamartoma and adenoma in the gastric epithelium; however, the role of BMP signaling in the progression of diffuse-type gastric carcinoma remains unknown. We investigated whether BMP functions as a tumor suppressor in human diffuse-type gastric carcinoma using three different human diffuse-type gastric carcinoma cell lines (OCUM-12, HSC-39, and OCUM-2MLN). Overexpression of the dominant-negative form of BMP-2/4-specific type I receptor (ALK-3) in OCUM-12 and HSC-39 cells accelerated their growth in vivo. BMP-4 induced cell cycle arrest in these cells via p21 induction through the SMAD pathway. Moreover, overexpression of the constitutively active form of ALK-3 in HSC-39 and OCUM-2MLN cells suppressed the proliferation of these cells in vitro and in vivo. Our findings suggest that BMP-2 and BMP-4 function as potent tumor suppressors in diffuse-type gastric carcinoma.
摘要
骨形态发生蛋白（BMP）信号缺陷与胃上皮的错构瘤和腺瘤形成之间存在关系；然而，BMP 信号在弥漫型胃癌的进展中的作用尚不清楚。我们使用三种不同的人弥漫型胃癌细胞系（OCUM-12、HSC-39 和 OCUM-2MLN）研究了 BMP 是否作为人弥漫型胃癌的肿瘤抑制因子发挥作用。在 OCUM-12 和 HSC-39 细胞中过表达 BMP-2/4 特异性 I 型受体（ALK-3）的显性失活形式加速了它们在体内的生长。BMP-4 通过 SMAD 通路诱导 p21 诱导使这些细胞发生细胞周期停滞。此外，在 HSC-39 和 OCUM-2MLN 细胞中过表达组成型激活形式的 ALK-3 可抑制这些细胞在体外和体内的增殖。我们的研究结果表明，BMP-2 和 BMP-4 在弥漫型胃癌中作为有效的肿瘤抑制因子发挥作用。
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本文引用的文献
1
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Oncogene. 2011 Apr 7;30(14):1693-705. doi: 10.1038/onc.2010.546. Epub 2010 Dec 6.
2
Somatic frameshift mutations of bone morphogenic protein receptor 2 gene in gastric and colorectal cancers with microsatellite instability.具有微卫星不稳定性的胃癌和结直肠癌中骨形态发生蛋白受体 2 基因的体细胞移码突变。
APMIS. 2010 Nov;118(11):824-9. doi: 10.1111/j.1600-0463.2010.02670.x. Epub 2010 Sep 2.
3
Autocrine TGF-β protects breast cancer cells from apoptosis through reduction of BH3-only protein, Bim.自分泌 TGF-β 通过减少 BH3 仅蛋白 Bim 来保护乳腺癌细胞免于凋亡。
J Biochem. 2011 Jan;149(1):55-65. doi: 10.1093/jb/mvq114. Epub 2010 Sep 29.
4
Bone morphogenetic protein signaling regulates gastric epithelial cell development and proliferation in mice.骨形态发生蛋白信号调节小鼠胃上皮细胞的发育和增殖。
Gastroenterology. 2010 Dec;139(6):2050-2060.e2. doi: 10.1053/j.gastro.2010.08.052. Epub 2010 Oct 16.
5
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6
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Nat Rev Cancer. 2010 Jun;10(6):415-24. doi: 10.1038/nrc2853.
7
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8
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J Biochem. 2010 Apr;147(4):545-54. doi: 10.1093/jb/mvp202. Epub 2009 Dec 2.
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