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Differentiation of cultured human breast cancer cells (AU‐565 and MCF‐7) associated with loss of cell surface HER‐2/neu antigen
Author(s) -
Bacus Sarah S.,
Kiguchi Kaoru,
Chin Dot,
King C. Richter,
Huberman Eliezer
Publication year - 1990
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940030607
Subject(s) - biology , immunostaining , microbiology and biotechnology , antigen , mcf 7 , monoclonal antibody , cancer cell , cytoplasm , cellular differentiation , cell culture , cell , extracellular , antibody , biochemistry , immunology , cancer , gene , immunohistochemistry , genetics , human breast
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), retinoicacid (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 μM MPA, 1.6 nM PMA, 2.5 μM RA, or 1 μg/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.