Therapeutic potential of S179D prolactin--from prostate cancer to angioproliferative disorders: the first selective prolactin receptor modulator.
Increasing evidence suggests an important role for autocrine/paracrine prolactin in breast and prostate cancers and other disease states. Prolactin production in these extrapituitary sites is not governed by dopamine agonists, a finding that has spurred the production of prolactin receptor antagonists. This review focuses on one such antagonist, S179D prolactin, which was produced by mimicking a natural antagonist, phosphorylated prolactin. S179D prolactin is a very effective growth antagonist, partly because it inhibits signalling from unmodified prolactin and partly because it produces its own intracellular signal. This signal results in cell differentiation, cell-cycle arrest or apoptosis depending on dose, duration of treatment and cellular context. S179D prolactin is also a potent antiangiogenic and initial studies have shown it to be a potent anti-inflammatory agent. In light of these additional modes of action, it is suggested that S179D prolactin should now be more aptly referred to as a selective prolactin receptor modulator.
Walker
Ameae M
AM
University of California, Division of Biomedical Sciences, Riverside, CA 92521, USA. Ameae.Walker@ucr.edu
D000818:Animals; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D011388:Prolactin / Q000494:pharmacology / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011981:Receptors, Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D011981:Receptors, Prolactin; C422171:prolactin, Asp(179)-; D011388:Prolactin