DIFFERENTIATION OF CULTURED HUMAN BREAST-CANCER CELLS (AU-565 AND MCF-7) ASSOCIATED WITH LOSS OF CELL-SURFACE HER-2/NEU ANTIGEN
DIFFERENTIATION OF CULTURED HUMAN BREAST-CANCER CELLS (AU-565 AND MCF-7) ASSOCIATED WITH LOSS OF CELL-SURFACE HER-2/NEU ANTIGEN
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DOI：
10.1002/mc.2940030607
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发表时间：
1990-01-01
影响因子：
4.6
通讯作者：
HUBERMAN, E
中科院分区：
文献类型：
--
作者：
BACUS, SS;KIGUCHI, K;HUBERMAN, E
在培养的人乳腺癌细胞中研究了终末细胞分化与HER-2/neu抗原亚细胞水平变化之间的关系：Au-565细胞（其过表达HER-2/neu基因）和MCF-7细胞（其不过表达该基因）。通过用霉酚酸（MPA）、佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）、视黄酸（RA）或针对HER-2/neu蛋白的细胞外结构域的TA-1单克隆抗体处理细胞来实现分化。在未经处理的、稀疏生长的Au-565培养物中，10%至20%的细胞表现出形态成熟，其特征在于大的花边状核被相当大的扁平细胞核包围。这些细胞中的一部分含有乳因子，如酪蛋白和大脂滴。用9 μ M MPA、1.6 nM PMA、2.5 μ M RA或1 μ g/mL TA-1抗体处理Au-565细胞4天，导致细胞生长抑制和表现出成熟表型的细胞百分比增加（48-97%）。MCF-7细胞也对MPA和RA的分化敏感，但程度低于Au-565细胞。在Au-565和MCF-7细胞中的分化与细胞表面膜上HER-2/neu蛋白的免疫染色减少和细胞质中该蛋白的弥散免疫染色短暂增加有关。
The relationship between terminal cell differentiation and changes in the subcellular levels of the HER-2/neu antigen was investigated in cultured human breast cancer cells: AU-565 cells (which overexpress the HER-2/neu gene) and MCF-7 cells (which do not overexpress this gene). Differentiation was achieved by treating the cells with mycophenolic acid (MPA), phorbol 12-myristate 13-acetate (PMA), retinoic acid (RA), or the TA-1 monoclonal antibody to the extracellular domain of the HER-2/neu protein. Ten to twenty percent of the cells in untreated, sparsely growing AU-565 cultures exhibited morphological maturation characterized by large lacy nuclei surrounded by sizable flat cytoplasms. A fraction of these cells harbored milk factors such as casein and large lipid droplets. Treatment of the AU-565 cells for 4 d with 9-mu-M MPA, 1.6 nM PMA, 2.5-mu-M RA, or 1-mu-g/mL TA-1 antibody resulted in cell growth inhibition and an increase in the percentage of cells (48-97%) that exhibit a mature phenotype. MCF-7 cells were also susceptible to differentiation by MPA and RA, but to a lesser degree than the AU-565 cells. Differentiation in the AU-565 and MCF-7 cells was associated with reduced immunostaining for the HER-2/neu protein at the cell surface membrane and with a transient increased diffuse immunostaining for this protein in the cytoplasm.