MWRI Work-in-Progress "A naturally occurring SRC-1 variant correlates with clinical bone loss, and increased osteoclast activity in a novel mouse model"

December 9, 2014
12:30 PM
Rebecca Watters, PhD
Postdoctoral Associate, Magee-Womens Research Institute
Magee-Women Research Institute, Conference Center, 1st Floor
Physician's earn 1.0 CME credits
Light lunch provided. Registration is not required.

Estrogen signaling plays a critical role in the etiology of breast cancer, but also is necessary for bone health and maintenance. In each of these tissues, estrogen signaling via the estrogen receptor is regulated by the nuclear co-factor SRC-1 (encoded by NCOA1), and there is published evidence that SRC-1 plays a role in both estrogen response in bone, and in breast cancer metastases. Given such dual roles of SRC-1 in the host (e.g. bone), and in tumor cell-intrinsic phenotypes, we hypothesize that SRC-1, and its naturally occurring genetic variants, are critical for bone metastases as well as normal bone development. Towards this goal, we have characterized a non-synonymous SNP in SRC-1(rs1804645; 2% MAF; P1272S) in activation domain 2 (AD2), which attenuates ER’s transcriptional activity of breast cancer cells in vitro. We recently finished generating a knock-in mouse model for this SNP, with the goal to characterize the effect of this variant on estrogen signaling, differentiation, and activation of individual bone cell types.