GREB1, short for Growth Regulation by Estrogen in Breast Cancer 1, is a gene significantly associated with steroid-hormone-related biological processes and various cancers. It acts as a critical mediator in the proliferation of breast and prostate cancer cells induced by estrogen and androgen respectively. GREB1 is also involved in pathways related to endometrial function, melanoma proliferation, and pancreatic β-cell proliferation [1,2,3,4,5]. Its function is linked to multiple signaling pathways such as the PI3K/Akt/mTOR pathway in breast cancer cells [4]. Genetic models, especially knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its functions in vivo.

In a β-cell-specific Greb1-deficient mouse model, Greb1 was shown to be essential for the recovery of depleted β cells in diabetic mice. This indicates that Greb1 plays a crucial role in pancreatic β-cell proliferation in diabetes [5]. In a BRAFV600E; PTENflox melanoma mouse model, targeting GREB1 Is4 (a splicing variant of GREB1) by antisense oligonucleotide decreased melanoma xenograft tumor formation, demonstrating its significance in melanoma proliferation [2].

In summary, Greb1 is vital in hormone-dependent cancer cell proliferation, endometrial function, and pancreatic β-cell proliferation. The use of KO/CKO mouse models has revealed its specific roles in diabetes-related pancreatic β-cell recovery and melanoma growth, providing potential therapeutic targets for these diseases.