In mouse and human studies of breast cancer metastatic to bone, they learned that bony metastases caused inflammation-related resorption with release of TGF-β and consequent upregulation of NADPH oxidase 4 (nox4) resulting in elevated oxidation of muscle proteins, including the ryanodine receptor calcium release channel 1 (RyR1). This evidence concerns the gene NOX4 and breast carcinoma.