Expression of oestrogen receptor-beta in oestrogen receptor-alpha negative human breast tumours.
To analyse the phenotype of breast tumours that express oestrogen receptor-beta (ERbeta) alone tissue microarrays were used to investigate if ERbeta isoforms are associated with specific prognostic markers and gene expression phenotypes in ERalpha-negative tumours. ERalpha-negative tumours were positive for ERbeta1 in 58% of cases (n=122/210), total ERbeta in 60% (n=115/192) and ERbeta2/cx in 57% of cases (n=114/199). Oestrogen receptor-beta1 and total ERbeta were significantly correlated with Ki67 (r=0.28, P<0.0001, n=209; r=0.29, P<0.0001, n=191) and with CK5/6, a marker of the basal phenotype (r=0.20, P=0.0106, n=170; r=0.18, P=0.0223, n=158). ERbeta2/cx was strongly associated with p-c-Jun and NF-kappaBp65 (r=0.53, P<0.0001, n=93; r=0.35, P<0.0001, n=176). This study shows that a range of ERbeta isoform expression occurs in ERalpha-negative breast tumours. While expression of ERbeta1, total and ERbeta2/cx are correlated, individual forms show associations with certain phenotypes that suggest different roles in subsets of ERalpha-negative cancers. Based on our in vivo observations, ERbeta may have the potential to become a therapeutic target in the specific subcohort of ERalpha-negative breast cancers.
Skliris
G P
GP
Department of Biochemistry & Medical Genetics, Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada R3E OV9.
Leygue
E
E
Curtis-Snell
L
L
Watson
P H
PH
Murphy
L C
LC
D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000172:deficiency*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015203:Reproducibility of Results; D016019:Survival Analysis; D017741:Survivors
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta