PMID: 11920638Mar 29, 2002Paper

Effect of prolonged hydroxytamoxifen treatment of MCF-7 cells on mitogen activated kinase cascade

International Journal of Cancer. Journal International Du Cancer
Fanjaniriana RabenoelinaEric Badia

Abstract

Resistance to the antiestrogen tamoxifen is the main stumbling block for the success of breast cancer therapy. We focused our study on cellular alterations induced by a prolonged treatment with the active tamoxifen metabolite hydroxytamoxifen (OHT). We show that a prolonged OHT treatment (for up to 7 days) led to a progressive increase in the level of phosphorylated p44/42 mitogen activated kinase (MAP kinase) induced by 10(-7) M TPA stimulation, without any significant change in the protein level. This effect was also observed in MCF-7 cells grown first in medium containing dextran-coated charcoal-treated FCS (DCC medium) for 20 days prior to OHT treatment, indicating a specific effect of the antiestrogen and not an effect of estrogen deprivation. It was prevented by cotreatment with estradiol and not observed in the estrogen receptor negative HeLa cell line, suggesting that it was mediated by the estrogen receptor. TPA induced phosphorylation of MEK1/2 was also raised by OHT treatment, without any change in their protein level or Raf-1 and H-Ras levels. When the MCF-7R OHT resistant cell line was grown in antiestrogen containing medium, the level of phosphorylated p44/42 MAP kinase was also high but reversed when the antiestr...Continue Reading

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Citations

Apr 20, 2004·Critical Reviews in Oncology/hematology·Sandra Timm Pearce, V Craig Jordan
Mar 7, 2003·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Petri LehenkariH Kalervo Väänänen
May 4, 2004·The Journal of Steroid Biochemistry and Molecular Biology·Abdelhabib SemlaliMarie-Josèphe Duchesne
Nov 23, 2006·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Syuichi MatsuyoshiNoboru Konishi

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