Abstract
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 anti-estrogens 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 lines. These pure anti-estrogens may thus be efficient second-line treatments of some Tamoxifen-resistant tumors.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antineoplastic Agents / pharmacology*
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / pathology
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Breast Neoplasms / ultrastructure
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Cathepsin D / genetics
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Cell Division / drug effects
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Drug Resistance
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Estradiol / analogs & derivatives*
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Estradiol / pharmacology
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Estrogen Antagonists / pharmacology*
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Estrogens / pharmacology
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Estrogens / physiology
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Fulvestrant
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Neoplasm Proteins / genetics
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Neoplasms, Hormone-Dependent / drug therapy*
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Neoplasms, Hormone-Dependent / pathology
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Neoplasms, Hormone-Dependent / ultrastructure
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Polyunsaturated Alkamides
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Proteins*
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Receptors, Estrogen / physiology
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Tamoxifen / analogs & derivatives*
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Tamoxifen / antagonists & inhibitors
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Tamoxifen / pharmacology
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Trefoil Factor-1
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Tumor Cells, Cultured
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Tumor Suppressor Proteins
Substances
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Antineoplastic Agents
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Estrogen Antagonists
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Estrogens
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Neoplasm Proteins
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Polyunsaturated Alkamides
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Proteins
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Receptors, Estrogen
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TFF1 protein, human
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Trefoil Factor-1
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Tumor Suppressor Proteins
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Tamoxifen
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afimoxifene
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Fulvestrant
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Estradiol
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ICI 164384
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Cathepsin D