Relationship of coregulator and oestrogen receptor isoform expression to de novo tamoxifen resistance in human breast cancer.
This study addresses the hypothesis that altered expression of oestrogen receptor-beta and/or altered relative expression of coactivators and corepressors of oestrogen receptors are associated with and may be mechanisms of de novo tamoxifen resistance in oestrogen receptor positive breast cancer. All cases were oestrogen receptor +, node negative, primary breast tumours from patients who later had no disease progression (tamoxifen sensitive) or whose disease progressed while on tamoxifen (tamoxifen resistant). Using an antibody to oestrogen receptor-beta that detects multiple forms of this protein (total) but not an antibody that detects only full-length oestrogen receptor-beta 1, it was found that high total oestrogen receptor beta protein expressors were more frequently observed in tamoxifen sensitive tumours than resistant tumours (Fisher's exact test, P=0.046). However, no significant differences in the relative expression of oestrogen receptor beta2, oestrogen receptor beta5 and full-length oestrogen receptor beta1 RNA in the tamoxifen sensitive and resistant groups were found. Also, when the relative expression of two known coactivators, steroid receptor RNA activator and amplified in breast cancer 1 RNA to the known corepressor, repressor of oestrogen receptor activity RNA, was examined, no significant differences between the tamoxifen sensitive and resistant groups were found. Altogether, there is little evidence for altered coregulators expression in breast tumours that are de novo tamoxifen resistant. However, our data provide preliminary evidence that the expression of oestrogen receptor beta protein isoforms may differ in primary tumours of breast cancer patients who prove to have differential sensitivity to tamoxifen therapy.
Murphy
L C
LC
Manitoba Institute of Cell Biology, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada, R3E OW3. lcmurph@cc.umanitoba.ca
Leygue
E
E
Niu
Y
Y
Snell
L
L
Ho
S-M
SM
Watson
P H
PH
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D047629:Estrogen Receptor beta; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007124:Immunoenzyme Techniques; D056921:Nuclear Receptor Coactivator 3; D016133:Polymerase Chain Reaction; D000091402:Prohibitins; D020033:Protein Isoforms / Q000378:metabolism; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D017931:DNA Primers; D047629:Estrogen Receptor beta; D000091402:Prohibitins; D020033:Protein Isoforms; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D022661:RNA, Untranslated; D011960:Receptors, Estrogen; D012097:Repressor Proteins; D014157:Transcription Factors; C405423:steroid receptor RNA activator; D013629:Tamoxifen; D056921:Nuclear Receptor Coactivator 3