BoneKEy Reports | BoneKEy Watch
A SNP in SRC-1 reduces bone density in tamoxifen-treated women
DOI:10.1038/bonekey.2012.117
In order to find out whether the effects of tamoxifen, an estrogen receptor (ER) modulator are influenced by the coregulator steroid receptor coactivator-1 (SRC-1), Hartmaier et al. investigated the impact of a single nucleotide polymorphism (SNP), which lies within the activation domain of SRC-1.
Several cell lines carrying this SNP were shown to be poor coactivators of ER compared with their corresponding wild-types. In vitro kinase assays and knock down experiments confirmed that the SNP is a Pro to Ser change in the β phosphorylation site of glycogen synthase 3.
This SNP also has clinical significance; women with the SNP who were treated with tamoxifen showed lower bone mineral density at the hip and the lumbar spine compared with women carrying the SRC-1 wild type gene. Since SRC-1 has been implicated as a factor in the metastasis of breast cancer, this SNP may also play a role in the establishment of bone metastases.
Editor's comment: A new approach to looking at the impact of a SNP; most studies look for genome-wide associations, but Hartmaier et al. investigated a SNP on the basis of biological activity. Detailed characterization allowed discovery of the nature of the change in the SRC-1 gene, and its impact was then demonstrated clinically.
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