ヒト乳癌培養細胞MCF-7におけるエストロゲン及び内分泌療法剤のestrogen receptor, progesterone receptor及びDNA合成能に与える影響:whole cell uptake法による検討

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In order to investigate the mechanisms of the endocrine therapeutic agents and the applicability of combined endocrine therapies for breast cancers, we studied the effects of estrogen and the endocrine therapeutic agents on estrogen receptor (ER), progesterone receptor (PgR), and DNA synthesis in MCF-7 human breast cancer cells, which is known to be sensitive to estrogen. ER and PgR of MCF-7 cells were determined by whole cell uptake method. In brief, intact MCF-7 cells cultured in the multi-well plates were incubated with various concentrations of tritiated estradiol (E2) or promegestone (R5020) at 37°C for 1 hour. The characteristics of the hormone binding were analyzed by Scatchard plots. MCF-7 cells had single class of ER (Kd : 2.1 ± 0.2 × 10-10M, MBC : 9.0 ± 1.5 × 103 sites/cell) and PgR (Kd : 7.2 ± 1.1 × 10-10M, MBC : 3.1 ± 0.5 X 104 sites/cell). When cultured in the presence of 10-8M or 10-6M of E2, tamoxifen (TAM), R5020 or medroxyprogesterone acetate (MPA) for 48 hrs, the numbers of binding sites of ER and PgR altered, but the affinities of either of them did not change. E2 (10-8 or 10-6M) increased about twice the number of PgR. Although treatment of 10-8M TAM, a non-steroidal antiestrogen, slightly increased the number of PgR, 10-6M TAM significantly decreased the number of PgR. Both of R5020 (10-8 or 10-6M) and MPA (10-8 or 10-6M), synthetic progestins, decreased the number of ER dose-dependently. On the other hand, E2 (1010-8 and 10-6M) and R5020 (10-8M) enhanced DNA synthesis, but 10-6M TAM or MPA inhibited DNA synthesis. The effects of single, sequential and coincidental treatment of these agents were compared. The sequential treatment of 10-8M E2 for 36 hrs and followed 10-6M MPA for 36 hrs ("10-8M E2→10-6 M MPA") and "10-6M TAM→10-6 M MPA" inhibited DNA synthesis of MCF-7 cells more efficiently than 10-6 M TAM alone or 10-6 M MPA alone for 72 hrs. However, "10-6M MPA→10-6M TAM" inhibited DNA synthesis less than "10-6M TAM→10-6M MPA". From these results, it is suggested that the MPA decreases the number of ER in breast cancer cells with the consequent result of the inhibition of the growth promoting effect of E2, and that the sequential administration of MPA after E2 or TAM may be more effective for the breast cancers sensitive for estrogen than the single administration of TAM or MPA alone.
一般社団法人日本内分泌学会の論文

ヒト乳癌培養細胞MCF-7におけるエストロゲン及び内分泌療法剤のestrogen receptor, progesterone receptor及びDNA合成能に与える影響:whole cell uptake法による検討

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