神经调节蛋白
生物
受体酪氨酸激酶
ErbB公司
癌症研究
受体
体内
细胞培养
细胞生长
内分泌学
生长因子
内科学
细胞生物学
信号转导
生物化学
医学
生物技术
遗传学
作者
Zuleima Aguilar,Robert W. Akita,Richard S. Finn,B Ramos,Mark D. Pegram,Fairooz Kabbinavar,Richard J. Pietras,Paul I. Pisacane,Mark X. Sliwkowski,Dennis J. Slamon
出处
期刊:Oncogene
[Springer Nature]
日期:1999-10-26
卷期号:18 (44): 6050-6062
被引量:142
标识
DOI:10.1038/sj.onc.1202993
摘要
The heregulins are a family of ligands with ability to induce phosphorylation of the p185HER-2/neu receptor. Various investigators have reported a variety of responses of mouse and human breast and ovarian cells to this family of ligands including growth stimulation, growth inhibition, apoptosis and induction of differentiation in cells expressing the HER-2/neu receptor. Some of the disparity in the literature has been attributed to variations in the cell lines studied, ligand dose applied, methodologies utilized or model system evaluated (i.e. in vitro or in vivo). To evaluate the effects of heregulin on normal and malignant human breast and ovarian epithelial cells expressing known levels of the HER-2/neu receptor, this report presents the use of several different assays, performed both in vitro and in vivo, in vitro proliferation assays, direct cell counts, clonogenicity under anchorage-dependent and anchorage-independent conditions, as well as the in vivo effects of heregulin on human cells growing in nude mice to address heregulin activity. Using a total of five different biologic assays in nine different cell lines, across two different epithelia and over a one log heregulin dose range, we obtained results that clearly indicate a growth-stimulatory role for this ligand in human breast and ovarian epithelial cells. We find no evidence that heregulin has any growth-inhibitory effects in human epithelial cells. We also quantitated the amount of each member of the type I receptor tyrosine kinase family (RTK I, i.e. HER-1, HER-2, HER-3 and HER-4) in the cell lines employed and correlated this to their respective heregulin responses. These data demonstrate that HER-2/neu overexpression itself affects the expression of other RTK I members and that cells expressing the highest levels of HER-2/neu have the greatest response to HRG.
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