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Expression of Sex Steroid Receptors and their Co-Factors in Normal and Malignant Breast Tissue: AIB1 is a Carcinoma-Specific Co-Activator

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Abstract

The differential expression pattern of estrogen receptor alpha (ER-α), estrogen receptor beta (ER-β) and their co-activator/co-repressor proteins is thought to modulate estrogenic action and to be present already during the early stages of tumorigenesis. It has therefore been postulated that certain co-activator and co-repressor proteins contribute to the development of breast cancer. There are some reports providing information on gene amplification and mRNA over-expression of certain co-factors in breast cancer, but to date there is only limited knowledge about their respective protein expressions. The aim of this study was to examine the expression of four steroid receptor co-activators (steroid receptor co-activator 1 (SRC-1), transcription intermediary factor 2 (TIF 2), protein 300 kDa/CREB binding protein (p300/CBP), amplified in breast cancer 1 (AIB1)), and of the co-repressor nuclear receptor co-repressor (NCoR), in malignant breast tissues and in matching normal breast biopsies of the same individuals. Protein expression was analyzed by immunohistochemistry and was compared to prognostic parameters such as lymph node involvement, tumor grading and receptor status. All members of the co-regulatory protein family were detected in both, benign and matching malignant tissue samples, except for AIB1, which was found to be expressed exclusively in malignant epithelium. AIB1 was preferentially present in carcinomas with high tumor grade (r = 0.48, p = 0.014), and was co-expressed with p300/CBP (r = 0.54, p = 0.006). TIF 2 correlated significantly to nodal status (r = 0.46, p = 0.025). Furthermore, protein levels of ER-β, p300/CBP and AIB1 were higher in invasive ductal carcinomas than in normal mammary tissue. The tumoral ER-α protein expression was significantly correlated with that of PgR (r = 0.61, p = 0.001) and NCoR (r = 0.4, p = 0.043), whereas ER-β expression was associated with SRC-1 (r = 0.68, p ≤ 0.001), TIF 2 (r = 0.64, p = 0.001) and NCoR (r = 0.48, p = 0.014) protein levels in malignant specimens. In our hands, 20% of ER-β positive tumors did not express ER-α protein, thereby suggesting that a substantial fraction of ER-beta positive tumors is falsely considered to be ‘estrogen receptor negative’ if only ER-α specific antibodies are employed in the histological assessment of the ER status.

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Authors and Affiliations

  1. Department of Senology and Ludwig Boltzmann-Institute of Clinical Experimental Oncology, University of Vienna, Vienna, Austria

    Gernot Hudelist, Ernst Kubista, Erika Marton & Christian F. Singer

  2. Department of Gynecopathology, University of Vienna, Vienna, Austria

    Klaus Czerwenka & Kerstin Pischinger

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  1. Gernot Hudelist
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  2. Klaus Czerwenka
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  3. Ernst Kubista
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  4. Erika Marton
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  6. Christian F. Singer
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Hudelist, G., Czerwenka, K., Kubista, E. et al. Expression of Sex Steroid Receptors and their Co-Factors in Normal and Malignant Breast Tissue: AIB1 is a Carcinoma-Specific Co-Activator. Breast Cancer Res Treat 78, 193–204 (2003). https://doi.org/10.1023/A:1022930710850

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