Initially, we examined the hyperglycemia-induced biology of orthotopically grown tumors from 3 ER– human breast cancer cell lines, MDA-MB-231, MDA-MB-468, and Hs578T, injected into the abdominal mammary fat pad of either diabetes-prone Akita mice (NOD.Cg-Rag1tm1Mom Ins2Akita Il2rgtm1Wjl/SzJ) or its matched control (NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ), all 8 weeks old. This evidence concerns the gene CTSG and diabetes mellitus.