Role of RNA binding protein HuR in ductal carcinoma in situ of the breast.

HuR is a ubiquitously expressed RNA-binding protein that modulates gene expression at the post-transcriptional level. It is predominantly nuclear, but can shuttle between the nucleus and the cytoplasm. While in the cytoplasm HuR can stabilize its target transcripts, many of which encode proteins involved in carcinogenesis. While cytoplasmic HuR expression is a marker of reduced survival in breast cancer, its role in precursor lesions of malignant diseases is unclear. To address this we explored HuR expression in atypical ductal hyperplasia (ADH) and in ductal in situ carcinomas (DCIS). We show that cytoplasmic HuR expression is elevated in both ADH and DCIS when compared to normal controls, and that this expression associated with high grade, progesterone receptor negativity and microinvasion and/or tumour-positive sentinel nodes of the DCIS. To study the mechanisms of HuR in breast carcinogenesis, HuR expression was silenced in an immortalized breast epithelial cell line (184B5Me), which led to reduction in anchorage-independent growth, increased programmed cell death and inhibition of invasion. In addition, we identified two novel target transcripts (CTGF and RAB31) that are regulated by HuR and that bind HuR protein in this cell line. Our results show that HuR is aberrantly expressed at early stages of breast carcinogenesis and that its inhibition can lead to suppression of this process. ArrayExpress Accession No. E-MEXP-3035.