Altered expression of estrogen receptor coregulators during human breast tumorigenesis.
The hypothesis that altered expression of specific coactivators/repressors of the estrogen receptor occurs during human breast tumorigenesis in vivo is examined in this study. Using in situ hybridization and reverse transcription-PCR assays, the expression of two coactivators (SRA and AIB1) and one repressor (REA) of the estrogen receptor was compared between matched breast tumors and adjacent normal human breast tissue. The levels of SRA and AIB1 mRNA were increased in tumors compared with normal tissues (n = 19; Wilcoxon matched pairs test; P < 0.01). In contrast, the expression of REA mRNA was not different between tumors and normal tissues (n = 19; Wilcoxon; P = 0.110). The ratios of AIB1:REA and SRA:REA were higher (Wilcoxon; P < 0.05) in tumors compared with normal tissues. Furthermore, SRA:AIB1 was higher (Wilcoxon; P = 0.0058) in tumors compared with normal tissues. Although our study is small, these data are consistent with the above hypothesis and suggest that such alterations may have a role in the altered estrogen action occurring during breast tumorigenesis.
Murphy
L C
LC
Department of Biochemistry and Medical Genetics, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada. lcmurph@cc.umanitoba.ca
Simon
S L
SL
Parkes
A
A
Leygue
E
E
Dotzlaw
H
H
Snell
L
L
Troup
S
S
Adeyinka
A
A
Watson
P H
PH
D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D056921:Nuclear Receptor Coactivator 3; D016612:Paraffin Embedding; D000091402:Prohibitins; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D022661:RNA, Untranslated / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000502:physiology; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; C000717331:PHB2 protein, human; D000091402:Prohibitins; 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; D012313:RNA; D056921:Nuclear Receptor Coactivator 3