Interaction between the adhesion receptor, CD44, and the oncogene product, p185(HER2), promotes human ovarian tumor cell activation
Interaction between the adhesion receptor, CD44, and the oncogene product, p185(HER2), promotes human ovarian tumor cell activation
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DOI：
10.1074/jbc.272.44.27913
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发表时间：
1997-10-31
影响因子：
4.8
通讯作者：
Hung, MC
中科院分区：
文献类型：
--
作者：
Bourguignon, LYW;Zhu, HB;Hung, MC
在这项研究中，我们研究了CD44s(标准型)和p185(HER2)原癌基因在卵巢癌细胞系中的相互作用。表面生物素化、麦胚凝集素柱层析和抗CD44介导的免疫沉淀表明CD44s和p185(HER2)都在细胞表面表达，最重要的是，这两个分子通过链间二硫键相互连接。我们还确定了透明质酸刺激CD44s相关的p185(HER2)酪氨酸激酶活性，导致卵巢癌细胞生长的增加。我们观察到，与对照细胞相比，转基因细胞表面CD44s的表达和CD44s介导的细胞与透明质酸的粘附性都显著降低。我们的研究结果还表明，CD44s-p185(HER2)的相互作用既是功能偶联的，又是生物合成调控的，我们认为这两个表面分子(即CD44s和p185(HER2))之间的直接“串扰”可能是人类卵巢癌发生发展中最重要的信号事件之一。
In this study we have examined the interaction between CD44s (the standard form) and the p185(HER2) proto-oncogene in the ovarian carcinoma cell line. Surface biotinylation followed by wheat germ agglutinin column chromatography and anti-CD44-mediated immunoprecipitation indicate that both CD44s and p185(HER2) are expressed on the cell surface and most importantly, that these two molecules are physically linked to each other via interchain disulfide bonds, We have also determined that hyaluronic acid stimulates CD44s-associated p185(HER2) tyrosine kinase activity, leading to an increase in the ovarian carcinoma cell growth,After transfection of the ovarian carcinoma cell line with the adenovirus 5 EIA gene, which is known to repress p185(HER2) expression, we observed that both surface CD44s expression and CD44s-mediated cell adhesion to hyaluronic acid are significantly reduced in the transfectant cells compared with the control cells. These data suggest that down-regulation of p185(HER2) blocks CD44s expression and subsequent adhesion function, Our findings also indicate that the CD44s-p185(HER2) interaction is both functionally coupled and biosynthetically regulated, We believe that direct ''cross-talk'' between these two surface molecules (i.e, CD44s and the p185(HER2)) may be one of the most important signaling events in human ovarian carcinoma development.