Document Detail


Elevated nuclear expression of the SMRT corepressor in breast cancer is associated with earlier tumor recurrence.
MedLine Citation:
PMID:  23015261     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), also known as nuclear corepressor 2 (NCOR2) is a transcriptional corepressor for multiple members of the nuclear receptor superfamily of transcription factors, including estrogen receptor-α (ERα). In the classical model of corepressor action, SMRT binds to antiestrogen-bound ERα at target promoters and represses ERα transcriptional activity and gene expression. Herein SMRT mRNA and protein expression was examined in a panel of 30 breast cancer cell lines. Expression of both parameters was found to vary considerably amongst lines and the correlation between protein and mRNA expression was very poor (R (2) = 0.0775). Therefore, SMRT protein levels were examined by immunohistochemical staining of a tissue microarray of 866 patients with stage I-II breast cancer. Nuclear and cytoplasmic SMRT were scored separately according to the Allred score. The majority of tumors (67 %) were negative for cytoplasmic SMRT, which when detected was found at very low levels. In contrast, nuclear SMRT was broadly detected. There was no significant difference in time to recurrence (TTR) according to SMRT expression levels in the ERα-positive tamoxifen-treated patients (P = 0.297) but the difference was significant in the untreated patients (P = 0.01). In multivariate analysis, ERα-positive tamoxifen-untreated patients with high nuclear SMRT expression (SMRT 5-8, i.e., 2nd to 4th quartile) had a shorter TTR (HR = 1.94, 95 % CI, 1.24-3.04; P = 0.004) while there was no association with SMRT expression for ERα-positive tamoxifen-treated patients. There was no association between SMRT expression and overall survival for patients, regardless of whether they received tamoxifen. Thus while SMRT protein expression was not predictive of outcome after antiestrogen therapy, it may have value in predicting tumor recurrence in patients not receiving adjuvant tamoxifen therapy.
Authors:
Carolyn L Smith; Ilenia Migliaccio; Vaishali Chaubal; Meng-Fen Wu; Margaret C Pace; Ryan Hartmaier; Shiming Jiang; Dean P Edwards; M Carolina Gutiérrez; Susan G Hilsenbeck; Steffi Oesterreich
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-09-27
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  136     ISSN:  1573-7217     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-17     Completed Date:  2013-05-23     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  253-65     Citation Subset:  IM    
Affiliation:
Department of Molecular & Cellular Biology, BCM130, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. carolyns@bcm.edu
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms* / drug therapy,  epidemiology,  metabolism,  pathology
Cell Line, Tumor
Cell Nucleolus / genetics,  metabolism
Estrogen Receptor alpha / metabolism
Female
Gene Expression Regulation, Neoplastic*
Humans
Middle Aged
Neoplasm Recurrence, Local / genetics,  metabolism,  pathology
Neoplasm Staging
Nuclear Receptor Co-Repressor 2 / genetics,  metabolism*
Survival Analysis
Tamoxifen / administration & dosage
Tissue Array Analysis
Grant Support
ID/Acronym/Agency:
DK53002/DK/NIDDK NIH HHS; P30CA125123/CA/NCI NIH HHS; P50CA058183/CA/NCI NIH HHS; R01 DK053002/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Estrogen Receptor alpha; 0/Nuclear Receptor Co-Repressor 2; 0/estrogen receptor alpha, human; 10540-29-1/Tamoxifen
Comments/Corrections

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