Timing is everything: order of administration of 5-aza 2' deoxycytidine, trichostatin A and tamoxifen changes estrogen receptor mRNA expression and cell sensitivity.
Restoration of estrogen receptor (ER) expression using epigenetic inhibitors re-establishes expression of the estrogen receptor (ER) and restores tamoxifen sensitivity in ER negative breast cancer cells. We tested if order of administration of the DNMT (5-aza 2' deoxycytidine/AZA) or HDAC (trichostatin A/TSA) inhibitors and tamoxifen affected ER re-expression and tamoxifen sensitivity. Treatment with AZA followed by co-administration of TSA plus tamoxifen resulted in the greatest ER re-expression and tamoxifen sensitivity, although sensitivity was not increased as robustly as expected. This could be due to increased cytoplasmic levels of HuR, suggesting that cytoplasmic HuR levels are central to tamoxifen responsiveness.
Hostetter
Christine L
CL
Department of Medicine, Robert Wood Johnson Medical, The University of Medicine and Dentistry of New Jersey, The Cooper Cancer Institute, 401 Haddon Avenue, Camden, NJ 08106, USA.
Licata
Lauren A
LA
Keen
Judith Clancy
JC
D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D000077209:Decitabine; D004334:Drug Administration Schedule; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*; D013629:Tamoxifen / Q000008:administration & dosage* / Q000494:pharmacology
D020847:Estrogen Receptor Modulators; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine