Abstract

Abstract Introduction: The p160 (SRC) family of estrogen receptor (ER) co-activators have important implications in tamoxifen resistance. The SRC family play a central role in ER mediated transcription. There are three family members; SRC-1, SRC-2 and AIB1. AIB1 is amplified in 5-10% of human breast cancers. SRC-1 expression is associated with HER2 expression, increased risk of recurrence and insensitivity to endocrine treatment. Co-factors interact with the ER and basal transcriptional machine to activate or repress ER-mediated transcription. To investigate the role of ER and its co-factors in breast cancer we have carried out quantitative RT-PCR (qRT-PCR) to measure the relative expression of ERa and its co-factors.Methods: In this study we examined patients which were untreated or treated with chemotherapy or hormonal therapy following breast conservation surgery. RNA was extracted from 340 early breast cancer specimens from the Edinburgh Breast Conserving Surgery cohort (BCS). The BCS is a fully documented consectutive cohort of breast cancers treated by conservation surgery, axillary node sampling or clearance, and whole breast radiotherapy between 1981-1998. Clinico-pathological features and complete follow up (duration >10 years) is available for this cohort. qRT-PCR was carried out using primers for ER, SRC-1, SRC-2, AIB1, NCoR1 and SMRT.Results: This study demonstrated SRC-1 expression to be negatively correlated with both SRC-2 and AIB1 expression. SRC-1 expression was also negatively correlated with the co-repressors NCoR1 and SMRT expression. There was a strong correlation between the co-repressors, NCoR1 and SMRT and the co-activators SRC-2 and AIB1. Relapse-free survival (RFS) was estimated using Kaplan-Meier curves. Patients who had high expression of all three co-activators had reduced relapse-free survival (HR: 2.15 95%C.I. 1.175-3.921, p=0.01). No significant association was noted with overall survival. Exploratory subgroup analysis was under powered and showed no significant association with outcome.Conclusion: In conclusion, our study of expression levels of ER and its cofactors by quantitative RT-PCR in breast cancer samples revealed a correlation between the co-factors and co-repressors. These findings would suggest that ER and cofactors may play a synergistic role in the development and progression of breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2127.

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