Our results point to the use of NCoR and TRβ as potential biomarkers for diagnosis or prognosis in breast cancer and suggest that further studies of these molecules as potential targets for anti-lymphangiogenic therapy are warranted.
In the present study, the level of expression of NCOR1 protein has been assessed by immunohistochemistry in 104 cases of invasive carcinoma of the breast.
Thus, we set out to identify novel single nucleotide polymorphisms (SNPs) within SRC-1 (NCoA1), SRC-3 (NCoA3, AIB1), NCoR (NCoR1), and SMRT (NCoR2), and test the most promising SNPs for associations with breast cancer risk.
Both primary tissue models and cancer cell lines displayed a spectrum of suppressed responsiveness towards 1alpha, 25 hydroxy vitamin D3 (1alpha25(OH)2D3) which correlated with elevated co-repressor content: specifically, elevated silencing mediator of retinoid and thyroid hormone receptors/nuclear co-repressor 2 (NCoR2/SMRT) in prostate cancer cell lines and primary tumour cultures, and elevated nuclear receptor co-repressor 1 (NCoR1) in breast cancer cell lines.
Increased NCoR1 mRNA is a novel molecular lesion in breast cancer cells, which acts to suppress responsiveness of VDR target genes, resulting in 1alpha,25(OH)(2)D(3) resistance and seems to be particularly associated with estrogen receptor negativity.