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. 2004 Feb 1;377(Pt 3):569–578. doi: 10.1042/BJ20030859

Prolactin stimulates cell proliferation through a long form of prolactin receptor and K+ channel activation.

Fabien Van Coppenolle 1, Roman Skryma 1, Halima Ouadid-Ahidouch 1, Christian Slomianny 1, Morad Roudbaraki 1, Philippe Delcourt 1, Etienne Dewailly 1, Sandrine Humez 1, Alexandre Crépin 1, Isabelle Gourdou 1, Jean Djiane 1, Jean-Louis Bonnal 1, Brigitte Mauroy 1, Natalia Prevarskaya 1
PMCID: PMC1223902  PMID: 14565846

Abstract

PRL (prolactin) has been implicated in the proliferation and differentiation of numerous tissues, including the prostate gland. However, the PRL-R (PRL receptor) signal transduction pathway, leading to the stimulation of cell proliferation, remains unclear and has yet to be mapped. The present study was undertaken to develop a clear understanding of the mechanisms involved in this pathway and, in particular, to determine the role of K(+) channels. We used androgen-sensitive prostate cancer (LNCaP) cells whose proliferation is known to be stimulated by PRL. Reverse transcriptase PCR analysis showed that LNCaP cells express a long form of PRL-R, but do not produce its intermediate isoform. Patch-clamp techniques showed that the application of 5 nM PRL increased both the macroscopic K(+) current amplitude and the single K(+)-channel open probability. This single-channel activity increase was reduced by the tyrosine kinase inhibitors genistein, herbimycin A and lavandustine A, thereby indicating that tyrosine kinase phosphorylation is required in PRL-induced K(+) channel stimulation. PRL enhances p59( fyn ) phosphorylation by a factor of 2 after a 10 min application in culture. In addition, where an antip59( fyn ) antibody is present in the patch pipette, PRL no longer increases K(+) current amplitude. Furthermore, the PRL-stimulated proliferation is inhibited by the K(+) channel inhibitors alpha-dendrotoxin and tetraethylammonium. Thus, as K(+) channels are known to be involved in LNCaP cell proliferation, we suggest that K(+) channel modulation by PRL, via p59( fyn ) pathway, is the primary ionic event in PRL signal transduction, triggering cell proliferation.

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Selected References

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