ANTI-EPIDERMAL GROWTH-FACTOR RECEPTOR ANTIBODIES INHIBIT THE AUTOCRINE-STIMULATED GROWTH OF MDA-468 HUMAN-BREAST CANCER-CELLS
ANTI-EPIDERMAL GROWTH-FACTOR RECEPTOR ANTIBODIES INHIBIT THE AUTOCRINE-STIMULATED GROWTH OF MDA-468 HUMAN-BREAST CANCER-CELLS
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DOI：
10.1210/mend-3-11-1830
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发表时间：
1989-11-01
影响因子：
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通讯作者：
DICKSON, RB
中科院分区：
文献类型：
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作者：
ENNIS, BW;VALVERIUS, EM;DICKSON, RB
研究了恶性和非恶性人类乳腺细胞系对表皮生长因子（EGF）受体单克隆抗体的生长抑制作用的反应。使用一系列表达EGF受体的人乳腺细胞系：MDA-468、MDA-231和Hs578T人乳腺癌细胞以及分别经过苯并[a]芘永生化并进一步用SV40T转化的转化人乳腺上皮细胞系184A1N4和184A1N4-T。测试了两种不同类别的四种抗体：225 免疫球蛋白 G (IgG)、108.4 IgG、96 免疫球蛋白 M (IgM) 和 42 IgM。所有四种抗体分别抑制 184A1N4 和 184A1N4-T 细胞的贴壁依赖性和非依赖性、EGF 刺激的生长，并且这种生长抑制可以通过添加浓度增加的 EGF 来逆转。相反，在没有外源EGF的情况下，抗体抑制MDA-468细胞的贴壁依赖性和非依赖性生长，这表明抗体起到阻断内源产生的配体接近EGF受体的作用。在抗体存在和 EGF 浓度增加的情况下，MDA-468 细胞的生长首先受到刺激，然后随着 EGF 浓度的增加而受到抑制，从而揭示了低浓度 EGF 对这些细胞的生长刺激潜力。数据表明 MDA-468 细胞分泌转化生长因子和自分泌生长刺激能力。含有激活的ras癌基因的MDA-231和Hs578T细胞的生长不受抗体的抑制，并且这些细胞系的生长也不受EGF的刺激。在所研究的细胞系中，只有 MDA-468 细胞似乎具有自分泌生长刺激能力。
The response of malignant and nonmalignant human breast cell lines to the growth inhibitory effects of monoclonal antibodies against the epidermal growth factor (EGF) receptor was studied. A series of human breast cell lines, which express EGF receptor, were used: MDA-468, MDA-231, and Hs578T human breast cancer cells and the transformed human mammary epithelial cell lines 184A1N4 and 184A1N4-T that have been benzo[a]pyrene immortalized and further transformed with SV40T, respectively. Four antibodies of two different classes were tested: 225 immunoglobulin G (IgG), 108.4 IgG, 96 immunoglobulin M (IgM), and 42 IgM. All four antibodies inhibited the anchorage-dependent and-independent, EGF-stimulated growth of 184A1N4 and 184A1N4-T cells, respectively, and this growth inhibition could be reversed by the addition of increasing concentrations of EGF. In contrast, the antibodies inhibited the anchorage-dependent and-independent growth of MDA-468 cells in the absence of exogenous EGF suggesting that the antibodies were acting to block access of an endogenously produced ligand to the EGF receptor. In the presence of antibody and increasing concentrations of EGF, MDA-468 cell growth was first stimulated then inhibited as the EGF concentration increased, thus, uncovering the growth stimulatory potential of low concentration of EGF in these cells. Data is presented that indicates MDA-468 cells secrete a transforming growth factor and autocrine growth stimulatory capabilities. The growth of MDA-231 and Hs578T cells, which contain activated ras oncogenes, was not inhibited by the antibodies and the growth of these cell lines was not stimulated by EGF. Of the cell lines studied only MDA-468 cells appear to possess an autocrine growth stimulatory capacity.