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BMC Cancer  2012 

Androgen receptor expression predicts breast cancer survival: the role of genetic and epigenetic events

DOI: 10.1186/1471-2407-12-132

Keywords: Androgen receptor, Prognostic biomarker, Breast cancer, Gene regulation, Promoter methylation, Regulatory mutation, MiRNA

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Abstract:

The levels of Androgen receptor protein in a cohort of breast tumour samples was determined by immunohistochemistry and the results were compared with clinical characteristics, including survival. The role of defects in the regulation of Androgen receptor gene expression were examined by mutation and methylation screening of the 5' end of the gene, reporter assays of the 5' and 3' end of the AR gene, and searching for miRNAs that may regulate AR gene expression.AR was expressed in 56% of tumours and expression was significantly inversely associated with 10-year survival (P = 0.004). An investigation into the mechanisms responsible for the loss of AR expression revealed that hypermethylation of the AR promoter is associated with loss of AR expression in breast cancer cells but not in primary breast tumours. In AR negative breast tumours, mutation screening identified the same mutation (T105A) in the 5'UTR of two AR negative breast cancer patients but not reported in the normal human population. Reporter assay analysis of this mutation however found no evidence for a negative impact on AR 5'UTR activity. The role of miR-124 in regulating AR expression was also investigated, however no evidence for this was found.This study highlights the potential for AR expression to be an informative biomarker for breast cancer survival and sets the scene for a more comprehensive investigation of the molecular basis of this phenomenon.Breast cancer is a heterogeneous disease comprising tumour subtypes associated with variable clinical characteristics [1]. Variables including tumour size, histological subtype and grade, lymph node status and the expression of estrogen receptor alpha (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) currently assist routine clinical management [2]. However, these factors are limited in their ability to predict individual survival and response to therapy [2]. This is particularly apparent for patients with advanced b

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