A progesterone derivative linked to a stable phospholipid activates breast cancer cell response without leaving the cell membrane

This work show that hormone action, which is assumed to act via binding to intracellular nuclear receptors, can also trigger a global cellular response acting on membrane bound receptors. We designed a progestrone-like compound attached to a phospholipid that cannot cross the cellular membrane, acting on membrane-attached progesterone receptors. Its signalling activates the MAP kinase pathway and reaches the nuclei, where its response is comparable to the natural hormonal response at the level of transcription, chromatin binding and cellular proliferation. These results are of widespread importance, not only for what it implies for the action of nuclear hormone receptors, but also because it identifies possible targets for clinical treatment of breast cancer patients at the cell membrane level. Examination of progesterone target genes activation via interaction of membrane-bound progesterone