GREB1, also known as Growth regulation by estrogen in breast cancer 1, is a key gene involved in steroid - hormone related biological processes. It serves as a critical mediator in the proliferation of various cancer cells including breast, ovarian, and prostate cancers. GREB1 is associated with multiple signaling pathways such as PI3K/Akt/mTOR, and it also participates in steroid - receptor feed - forward mechanisms [1,3,4,6]. Genetic models, especially KO/CKO mouse models, are valuable tools for studying its functions.

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, suggesting its role in pancreatic β - cell proliferation [5]. In melanoma, silencing of a GREB1 splicing variant (isoform 4) reduced melanoma cell proliferation in vitro, and targeting it by antisense oligonucleotide decreased melanoma xenograft tumor formation in a mouse model, highlighting its importance in melanoma proliferation [2]. In hepatoblastoma, depletion of GREB1 in a mouse model with liver tumors strongly suppressed marker gene expression and tumorigenesis, indicating its role in promoting hepatoblastoma development [7].

In conclusion, GREB1 plays essential roles in hormone - dependent cancer proliferation, pancreatic β - cell proliferation, and melanoma development. The use of KO/CKO mouse models has significantly contributed to understanding its functions in these disease areas, providing insights into potential therapeutic targets for hormone - responsive cancers, diabetes, and melanoma.