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Elevated nuclear expression of the SMRT corepressor in breast cancer is associated with earlier tumor recurrence

  • Epidemiology
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Abstract

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.

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Acknowledgments

This work was supported by the National Institutes of Health (DK53002 to CLS, and a SPORE Pilot Project P50CA058183 to SO), the Department of Defense (W81XWH-08-1-0586 to CLS), the American Cancer Society (PF-07-233-01-TBE to MCP), the Proteomics and Biostatistics & Informatics Cores of the NCI Cancer Center Support Grant (P30CA125123) and the Breast Cancer SPORE Grant (P50CA058183).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular & Cellular Biology, BCM130, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    Carolyn L. Smith, Vaishali Chaubal, Margaret C. Pace, Dean P. Edwards & Steffi Oesterreich

  2. Department of Urology, Baylor College of Medicine, Houston, TX, 77030, USA

    Carolyn L. Smith

  3. Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, 77030, USA

    Dean P. Edwards & M. Carolina Gutiérrez

  4. Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Ilenia Migliaccio, Ryan Hartmaier, Shiming Jiang, M. Carolina Gutiérrez, Susan G. Hilsenbeck & Steffi Oesterreich

  5. Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Meng-Fen Wu & Susan G. Hilsenbeck

  6. The Women’s Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA

    Steffi Oesterreich

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  1. Carolyn L. Smith
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Correspondence to Carolyn L. Smith.

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Smith, C.L., Migliaccio, I., Chaubal, V. et al. Elevated nuclear expression of the SMRT corepressor in breast cancer is associated with earlier tumor recurrence. Breast Cancer Res Treat 136, 253–265 (2012). https://doi.org/10.1007/s10549-012-2262-7

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  • DOI: https://doi.org/10.1007/s10549-012-2262-7

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