ANTIPROLIFERATIVE AND ANTIESTROGENIC EFFECTS OF ICI 164,384 AND ICI 182,780 IN 4-OH-TAMOXIFEN-RESISTANT HUMAN BREAST-CANCER CELLS
ANTIPROLIFERATIVE AND ANTIESTROGENIC EFFECTS OF ICI 164,384 AND ICI 182,780 IN 4-OH-TAMOXIFEN-RESISTANT HUMAN BREAST-CANCER CELLS
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DOI：
10.1002/ijc.2910560225
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发表时间：
1994-01-15
影响因子：
6.4
通讯作者：
ROCHEFORT, H
中科院分区：
文献类型：
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作者：
COOPMAN, P;GARCIA, M;ROCHEFORT, H
抗雌激素4-羟他莫昔芬（OHTam）， ICI 164,384和。在MCF-7/LCC2乳腺癌细胞系上检测ICI 182780，该细胞系在OHTam存在下显著生长，可作为研究雌激素受体阳性乳腺癌抗雌激素耐药的模型。ICI 182780或ICI 164384单独使用或ICI 164384与17- β -雌二醇（E2）或OHTam联合使用均能强烈抑制细胞增殖和cathepsin-D分泌。单独的ICI 164,384不影响cathepsin-D和pS2 mRNA水平，但可以拮抗E2或OHTam对这2种mRNA的刺激作用。OHTam在增加cathepsin-D mRNA水平方面比E2更有效，这支持了抗雌激素抵抗乳腺癌持续过度表达cathepsin-D的观点。这些数据表明，甾体抗雌激素ICI 164,384和ICI 182,780在ohtam耐药MCF-7/LCC2细胞系中保留了抑制细胞增殖和cathepsin-D和pS2基因雌激素反应的能力。因此，这些纯抗雌激素可能是一些他莫昔芬耐药肿瘤的有效二线治疗方法。(C) 1994 Wiley-Liss, Inc。
The effects of the anti-estrogens 4-hydroxytamoxifen (OHTam), ICI 164,384 and.ICI 182,780 were tested on the MCF-7/LCC2 breast-carcinoma cell line, which grows significantly in the presence of OHTam and serves as a model for studying anti-estrogen resistance of estrogen-receptor-positive breast cancer. Cell proliferation and cathepsin-D secretion were strongly inhibited by either ICI 182,780 or ICI 164,384 alone or ICI 164,384 in combination with 17-beta-estradiol (E2) or OHTam. ICI 164,384 alone did not affect the cathepsin-D and pS2 mRNA levels, but antagonized the stimulatory effects of E2 or OHTam on these 2 mRNAs. OHTam was more effective than E2 in increasing cathepsin-D mRNA levels, supporting the idea that anti-estrogen-resistant breast cancer continues to overexpress cathepsin-D. These data show that the steroidal antiestrogens ICI 164,384 and ICI 182,780 retain their ability to inhibit cell proliferation and the estrogen-responsiveness of cathepsin-D and pS2 genes in the OHTam-resistant MCF-7/LCC2 cell line. These pure anti-estrogens may thus be efficient second-line treatments of some Tamoxifen-resistant tumors. (C) 1994 Wiley-Liss, Inc.