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The author established three variant cell lines which were proliferative in the serum-free medium. These three cell lines were derived from MCF-7, a human breast cancer cell line. These 3 variants (MCF-S1, MCF-S2 and MCF-S3) proliferate estrogen (E2)-dependently, but the amounts of E2 receptor and progesterone receptor in the cells are different from each other among the variants. The author compared the effects of hormonal therapeutic agents, tamoxifen (TAM), 3-hydroxytamoxifen (3-OH-TAM), toremifene (TORE), and medroxyprogesterone acetate (MPA) on MCF-7 and the established variant cells. Although TAM showed little effect on the growth of any cell lines in the absence of E2, it considerably inhibited the growth of MCF-S2 cells and MCF-7 cells in the presence of 10(-10)M E2. TORE also provided no inhibitory effect at less than 10(-7)M concentration on any cells in the absence of E2, but it dose-dependently inhibited DNA synthesis of MCF-S2 cells in the presence of E2. On the other hand, although 3-OH-TAM markedly inhibited the growth of any cell lines at a concentration of less than 10(-6)M in the presence of E2, it dose-dependently inhibited the DNA synthesis of any cell lines in the absence of E2, and the effect was remarkable in the case of MCF-S2 or MCF-S3. MPA showed a tendency to increase the proliferation of any cells in the absence of E2, conversely in the presence of E2, and it slightly inhibited DNA synthesis at concentrations of over 10(-8)M. These results suggest that the effect of hormonal agents on breast cancer cells may depend on either hormonal levels or the characteristics of the cancer cells. The effect of the hormonal agents are diverse, and a hormonal agent which does not work well on one cancer cell population may work well on another population.

The Diverse Effects of Hormonal Therapeutic Agents on the Proliferations of Human Breast Cancer Cell Lines, MCF-7 and its Variants