Expression of heregulin α, erbB2, and erbB3 and their influences on proliferation of gastric epithelial cells
Expression of heregulin α, erbB2, and erbB3 and their influences on proliferation of gastric epithelial cells
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DOI：
10.1016/s0016-5085(99)70397-5
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发表时间：
1999-11-01
期刊：
影响因子：
29.4
通讯作者：
Kasuga, M
中科院分区：
文献类型：
--
作者：
Noguchi, H;Sakamoto, C;Kasuga, M
背景与目的：Heregulins(Heregulins，HRGs)调节多种细胞类型的增殖和分化。然而，人们对它们在胃肠道中的作用知之甚少。本研究的目的是研究HRGs对胃肠道细胞的作用。方法：采用Western印迹分析和逆转录聚合酶链式反应方法检测了人胃癌细胞系、大鼠胃肠道上皮细胞和人胃成纤维细胞中erbB受体和HRG-α的表达。Western印迹分析检测HRG-α诱导的受体磷酸化和异二聚化。我们还评估了HRG-α在体外对细胞增殖和修复的影响。结果：癌细胞株和大鼠上皮细胞表达erbB2和erbB3，未检测到erBB4蛋白的表达。HRG-α仅在胃成纤维细胞中表达。HRG-α激活了表皮生长因子受体(EGFR)、erbB2和erbB3的酪氨酸磷酸化，不仅诱导了erbB3/erbB2，而且还诱导了MKN-28癌细胞中erbB3/EGFR和erbB2/EGFR异源二聚体的形成。MKN-28细胞与胃成纤维细胞同时培养后，MKN-28细胞中的erbB3酪氨酸磷酸化。HRG-α还能刺激MKN-28细胞和胃上皮细胞的增殖。结论：HRG-α可能通过间质-上皮相互作用影响胃粘膜上皮细胞的增殖。
Background & Aims: Heregulins (HRGs) regulate the proliferation and differentiation of various cell types. However, very little is known about their function in the gastrointestinal tract. The aim of this study was to investigate the role of HRGs on gastrointestinal cells. Methods: We examined the expression of erbB receptors and HRG-alpha in human gastric cancer cell lines, rat gastrointestinal epithelial cells, and human gastric fibroblasts by Western blot analysis or reverse-transcription polymerase chain reaction. Receptor phosphorylation and heterodimerization induced by HRG-alpha were detected by Western blot analysis. We also evaluated the in vitro effects of HRG-alpha on cell proliferation and restitution. Results: Cancer cell lines and rat epithelial cells expressed erbB2 and erbB3, but protein expression of erbB4 was not detected. HRG-alpha was detected only in gastric fibroblasts. HRG-alpha activated tyrosine phosphorylation of epidermal growth factor receptor (EGFR), erbB2, and erbB3 and induced not only erbB3/erbB2 but also erbB3/EGFR and erbB2/EGFR heterodimer formation in MKN-28 cancer cells. Simultaneous cultivation of MKN-28 cells with gastric fibroblasts resulted in tyrosine phosphorylation of erbB3 in MKN-28 cells. HRG-alpha also stimulated proliferation of MKN-28 cells and gastric epithelial cells. Conclusions: The data suggest that HRG-alpha may affect epithelial cell proliferation through mesenchymal-epithelial interaction in the gastric mucosa.