BMP-2 modulates the proliferation and differentiation of normal and cancerous gastric cells

BMP-2 modulates the proliferation and differentiation of normal and cancerous gastric cells
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DOI:
10.1016/j.bbrc.2004.02.016
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发表时间:
2004-03-26
影响因子:
3.1
通讯作者:
Yuasa, Y
Yuasa, Y
中科院分区:
生物学4区
文献类型:
--
作者:
Wen, XZ;Miyake, S;Yuasa, Y

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骨形态发生蛋白2(BMP-2)是转化生长因子β超家族的一员,已被证明通过激活引起细胞周期停滞的信号级联而作为多种细胞系的抗增殖剂。然而,BMP-2对胃细胞的生物学效应和作用机制尚不清楚。在本研究中,我们发现重组人BMP-2剂量依赖性地抑制OUMS 37大鼠胃细胞和MKN 74人胃癌细胞的生长。流式细胞仪分析显示,这种抗增殖作用可能是由于细胞周期阻滞在G(1)期所致。BMP-2增加p21/WAF 1/CIP 1的水平,表明BMP-2介导的细胞增殖抑制可能通过p21/WAF 1/CIP 1诱导。此外,BMP-2增加了MKN 74细胞中胃蛋白酶原II(胃的分化标记物)的表达。这些结果表明,BMP-2在调节胃上皮细胞的增殖和分化中起重要作用。(C)2004年爱思唯尔公司All rights reserved.
Bone morphogenetic protein 2 (BMP-2), a member of the transforming growth factor beta super-family, has been shown to act as an antiproliferative agent for a variety of cell lines by activating signaling cascades that cause cell cycle arrest. However, the biological effect and mechanism of action of BMP-2 on gastric cells remain unknown. In the present study, we showed that recombinant human BMP-2 dose-dependently inhibited the growth of OUMS37 rat gastric cells and MKN74 human gastric cancer cells. The antiproliferation seems to be due to cell cycle arrest in the G(1)-phase, which was revealed by flow cytometric assays. BMP-2 increased the level of p21/WAF1/CIP1, suggesting that BMP-2-mediated inhibition of cell proliferation may be induced through p21/WAF1/CIP1. In addition, BMP-2 increased the expression of pepsinogen II, a differentiation marker of the stomach, in MKN74 cells. These results indicate that BMP-2 plays important roles in modulating the proliferation and differentiation of gastric epithelial cells. (C) 2004 Elsevier Inc. All rights reserved.