B67
Expression levels of ERα and co-factors in early breast cancer
Melanie Spears1, Johanna Pedraza1, Jeremy Thomas2, Gillian Kerr2, Wilma Jack2, Fiona Campbell1, Laura McKay1, Ian Kunkler2, David Cameron3, Udi Chetty2, John Bartlett1
1University of Edinburgh, UK, 2Western General Hospital, Edinburgh, UK, 3University of Leeds, UK
Background
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 to measure the relative expression of ERα and its co-factors.
Method
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. 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 (p=0.03).
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 synergistical role in the development and progression of breast cancer.
