Modulation of oestrogen action by receptor gene inhibition.
Selective oestrogen receptor downregulators (SERDs) are a class of highly effective steroidal antitumour agents that reduce cellular levels of the oestrogen receptor (ER). In this study, we compared the efficacy by which three novel molecular approaches: (1) antisense oligonucleotides; (2) antisense RNA; and (3) dominant negative mutants are able to act as SERDs. Using transient and, where appropriate, stable gene transfection experiments we found that constitutive overexpression of ER antisense RNA and a hormone-binding domain compromised dominant-negative ER mutant (DNER-1), were most effective at downregulating ER expression and/or activity in vitro.
Madden
T A
TA
Tenovus Cancer Research Centre, Welsh School of Pharmacy, Redwood Building, King Edward VII Ave, CF10 3XE, Cardiff, UK. maddenta1@cardiff.ac.uk
Barrow
D
D
McClelland
R A
RA
Gee
J M
JM
Nicholson
R I
RI
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015152:Blotting, Northern; D002455:Cell Division; D002478:Cells, Cultured; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D000077267:Fulvestrant; D017930:Genes, Reporter; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D016376:Oligonucleotides, Antisense; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D000077267:Fulvestrant; D004958:Estradiol