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Human breast cancer cell lines resistant to pure anti‐estrogens are sensitive to tamoxifen treatment
Author(s) -
Lykkesfeldt Anne E.,
Larsen Søren S.,
Briand Per
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910610417
Subject(s) - tamoxifen , estrogen receptor , estrogen , cell culture , antiestrogen , mcf 7 , endocrinology , medicine , biology , cell growth , growth inhibition , receptor , mammary gland , cancer cell , breast cancer , cancer , human breast , biochemistry , genetics
The pure steroidal anti‐estrogens ICI 164,384 and ICI 182,780 are very potent growth inhibitors of the estrogen receptor‐positive human breast cancer cell line MCF‐7. However, long‐term treatment of MCF‐7 cells with 10 −7 M concentrations of these compounds results in selection of proliferating colonies of resistant cells. Our report describes 4 ICI 164,384‐ and 3 ICI 182,780‐resistant MCF‐7 sublines established after long‐term treatment. Resistant sublines are estrogen receptor‐positive, and all sublines have lost expression and estrogen inducibility of the progesterone receptor protein. Based on IC 50 concentrations, all tested resistant sublines had a reduced sensitivity to pure anti‐estrogens on the order of 100‐ to 1000‐fold compared with parent MCF‐7 cells. All resistant cell lines have survived propagation for more than 15 subcultivations in the presence of 10 −7 M pure anti‐estrogen. The MCF‐7/182 R ‐6 subline has been tested for stability of resistance and appeared to be stably resistant after 13 weeks of propagation without the selective pressure of ICI 182,780. Cell lines resistant to the ICI 182,780 compound are cross‐resistant to the ICI 164,384 compound and vice versa. However, the sublines resistant to pure anti‐estrogens are sensitive to tamoxifen. Our results show that although the pure steroidal anti‐estrogens are very potent growth inhibitors, they do not circumvent development of resistance. © 1995 Wiley‐Liss, Inc .