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receptor protein binding effect analog vitamin activity estrogen cancer ligand mouse osteocalcin study kh 1060 wound response change serum metabolite element growth peptide expression dihydroxyvitamin therapy exosome biochem figure transcription tumor interaction ros 17/2.8 cells analysis van leeuwen jptm level breast prostate factor affinity estrogen receptor proteasome potency tissue pols hap action 17/2.8 sequence tamoxifen difference domain bone resorption protease activation osteopontin compound transcriptional result nucleotide treatment table assay khi 060 differentiation calcium endocrinology concentration regulation osteoblast-like mechanism patient addition hormone vacuum therapy stability sample leeuwen endocrinol half-site control kinase