Therapeutic potential of S179D prolactin – from prostate cancer to angioproliferative disorders: the first selective prolactin receptor modulator

Abstract

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.

Keywords::

• antiangiogenic
• anti-inflammatory
• breast cancer
• prolactin
• prostate cancer
• S179D prolactin
• SPeRM

Acknowledgements

The author apologises to all investigators whose pertinent original publications may not have been cited. The breadth of coverage necessitated the use of broader references in preference to the first and/or individual reports.

The author thanks the many talented individuals (past and present) from her own laboratory and from other laboratories who have contributed in various ways to the development and analysis of S179D prolactin. Recent work in the laboratory has been primarily supported by National Institutes of Health grant NIDDK 61005, California Breast Cancer Research Programme grant 10PB-0127 and an award from the Prostate Cancer Foundation.

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