Structure and function of epigen, the last EGFR ligand

• Epigen is the latest addition to the mammalian family of EGFR ligands, which includes six other growth factors.
• Despite low affinity binding to EGFR, sub-maximal receptor activation by epigen delivers strong mitogenic signals.
• Similarly to the other EGFR ligands, the expression of epigen is up-regulated by hormones and in certain cancer types.
• Epigen functions in epidermal structures, such as the sebaceous gland, which was enlarged in mice overexpressing epigen.
• Mice lacking epigen develop and grow normally, probably due to functional compensation by other EGFR ligands.

Epigen is the latest addition to the mammalian family of EGFR ligands. Epigen was initially identified as a novel expressed sequence tag with homology to the EGF family by high throughput sequencing of a mouse keratinocyte complementary DNA library, and received its name for its ability to act as an epithelial mitogen. In vitro studies attributed to epigen several unique features, such as persistent and potent biological actions involving low affinity receptor binding, as well as sub-maximal receptor activation and inactivation. Similarly to the other EGFR ligands, the expression of epigen is up-regulated by hormones and in certain cancer types. While the biological functions of epigen remain to be uncovered, it appears to play a role in epidermal structures, such as the mammary gland and the sebaceous gland. The latter organ, in particular, was greatly enlarged in transgenic mice overexpressing epigen. Interestingly, mice lacking epigen develop and grow normally, probably due to functional compensation by other EGFR ligands. Future studies are likely to reveal the biological roles of the unique receptor binding properties of epigen, as well as its potential harnessing during disease.