Anti-oestrogen resistant human breast cancer cell lines are more sensitive towards treatment with the vitamin D analogue EB1089 than parent MCF-7 cells.
Most breast cancer patients treated with anti-oestrogens will eventually develop resistance towards treatment. Therefore it is important to find new therapeutic agents effective for treatment of patients relapsing on anti-oestrogen. The vitamin D analogue EB1089 (Seocalcitol(TM)) is a promising new agent for treatment of breast cancer patients with advanced disease, and in this study we show that two different anti-oestrogen-resistant human breast cancer cell lines are more sensitive towards treatment with EB1089, than the parent MCF-7 cell line. The two resistant cell lines both express a lower content of the anti-apoptotic protein Bcl-2, and we suggest that this may explain the higher sensitivity towards EB1089. The importance of Bcl-2 for response to EB1089 is supported by our observation that oestradiol abrogates the effect of EB1089 in cell lines which increase Bcl-2 in response to oestradiol treatment. Overall these results indicate that treatment with Seocalcitol(TM)may prove effective when patients become refractory to anti-oestrogen therapy, and that Bcl-2 may be used as a predictive marker.
Department of Tumor Endocrinology, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, Copenhagen, DK-2100 Ø, Denmark.
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Larsen
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Heiberg
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Lykkesfeldt
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D004351:Drug Resistance; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; D002117:Calcitriol; C078903:seocalcitol