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 p59fyn phosphorylation by a factor of 2 after a 10 min application in culture. In addition, where an antip59fyn 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 α-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 p59fyn pathway, is the primary ionic event in PRL signal transduction, triggering cell proliferation.
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February 2004
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Research Article|
February 01 2004
Prolactin stimulates cell proliferation through a long form of prolactin receptor and K+ channel activation
Fabien VAN COPPENOLLE;
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
2To whom correspondence should be addressed (e-mail [email protected]).
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Roman SKRYMA;
Roman SKRYMA
1
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Halima OUADID-AHIDOUCH;
Halima OUADID-AHIDOUCH
3
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Christian SLOMIANNY;
Christian SLOMIANNY
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Morad ROUDBARAKI;
Morad ROUDBARAKI
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Philippe DELCOURT;
Philippe DELCOURT
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Etienne DEWAILLY;
Etienne DEWAILLY
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Sandrine HUMEZ;
Sandrine HUMEZ
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Alexandre CRÉPIN;
Alexandre CRÉPIN
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Isabelle GOURDOU;
Isabelle GOURDOU
†Laboratory of Molecular Endocrinology, INRA, Jouy en Josas, France
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Jean DJIANE;
Jean DJIANE
†Laboratory of Molecular Endocrinology, INRA, Jouy en Josas, France
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Jean-Louis BONNAL;
Jean-Louis BONNAL
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Brigitte MAUROY;
Brigitte MAUROY
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Natalia PREVARSKAYA
Natalia PREVARSKAYA
*Laboratoire de Physiologie Cellulaire, INSERM EMI 0228, Université des Sciences et Technologies de Lille, Bât. SN3, 59655 Villeneuve d'Ascq Cedex, France
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Publisher: Portland Press Ltd
Received:
June 10 2003
Revision Received:
October 16 2003
Accepted:
October 17 2003
Accepted Manuscript online:
October 17 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 377 (3): 569–578.
Article history
Received:
June 10 2003
Revision Received:
October 16 2003
Accepted:
October 17 2003
Accepted Manuscript online:
October 17 2003
Citation
Fabien VAN COPPENOLLE, Roman SKRYMA, Halima OUADID-AHIDOUCH, Christian SLOMIANNY, Morad ROUDBARAKI, Philippe DELCOURT, Etienne DEWAILLY, Sandrine HUMEZ, Alexandre CRÉPIN, Isabelle GOURDOU, Jean DJIANE, Jean-Louis BONNAL, Brigitte MAUROY, Natalia PREVARSKAYA; Prolactin stimulates cell proliferation through a long form of prolactin receptor and K+ channel activation. Biochem J 1 February 2004; 377 (3): 569–578. doi: https://doi.org/10.1042/bj20030859
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