Hudziak R M, Lewis G D, Winget M, Fendly B M, Shepard H M, Ullrich A
Department of Developmental Biology, Genentech, Inc., South San Francisco, California 94080.
Mol Cell Biol. 1989 Mar;9(3):1165-72. doi: 10.1128/mcb.9.3.1165-1172.1989.
The HER2/c-erbB-2 gene encodes the epidermal growth factor receptorlike human homolog of the rat neu oncogene. Amplification of this gene in primary breast carcinomas has been show to correlate with poor clinical prognosis for certain cancer patients. We show here that a monoclonal antibody directed against the extracellular domain of p185HER2 specifically inhibits the growth of breast tumor-derived cell lines overexpressing the HER2/c-erbB-2 gene product and prevents HER2/c-erbB-2-transformed NIH 3T3 cells from forming colonies in soft agar. Furthermore, resistance to the cytotoxic effect of tumor necrosis factor alpha, which has been shown to be a consequence of HER2/c-erbB-2 overexpression, is significantly reduced in the presence of this antibody.
HER2/c-erbB-2基因编码大鼠神经癌基因的表皮生长因子受体样人类同源物。原发性乳腺癌中该基因的扩增已被证明与某些癌症患者的不良临床预后相关。我们在此表明,一种针对p185HER2细胞外结构域的单克隆抗体可特异性抑制过表达HER2/c-erbB-2基因产物的乳腺肿瘤衍生细胞系的生长,并阻止HER2/c-erbB-2转化的NIH 3T3细胞在软琼脂中形成集落。此外,在该抗体存在的情况下,对肿瘤坏死因子α细胞毒性作用的抗性(已证明这是HER2/c-erbB-2过表达的结果)显著降低。