Prolactin stimulates cell proliferation through a long form of prolactin receptor and K+ channel activation
| Autor: | Halima Ouadid-Ahidouch, Christian Slomianny, Natalia Prevarskaya, Roman Skryma, Etienne Dewailly, Jean Djiane, Philippe Delcourt, Morad Roudbaraki, Brigitte Mauroy, Isabelle Gourdou, Fabien Van Coppenolle, Alexandre Crepin, Sandrine Humez, Jean-Louis Bonnal |
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| Přispěvatelé: | Neurobiologie de l'Olfaction et de la Prise Alimentaire (NOPA), Institut National de la Recherche Agronomique (INRA), ProdInra, Migration |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Male
Patch-Clamp Techniques Potassium Channels [SDV]Life Sciences [q-bio] Proto-Oncogene Proteins c-fyn Biochemistry Membrane Potentials 0302 clinical medicine Cytosol CANAL POTASSIQUE Protein Isoforms Phosphorylation Receptor ComputingMilieux_MISCELLANEOUS 0303 health sciences CANCER 3. Good health Cell biology Neoplasm Proteins [SDV] Life Sciences [q-bio] 030220 oncology & carcinogenesis Signal transduction Tyrosine kinase Ion Channel Gating hormones hormone substitutes and hormone antagonists Cell Division Research Article Signal Transduction medicine.medical_specialty endocrine system Receptors Prolactin RT-PCR Biology [INFO] Computer Science [cs] 03 medical and health sciences FYN Internal medicine Cell Line Tumor Proto-Oncogene Proteins LNCaP medicine Humans [INFO]Computer Science [cs] Molecular Biology 030304 developmental biology Cell growth Prolactin receptor Cell Biology Prolactin Endocrinology CULTURE DE CELLULE Calcium |
| Zdroj: | Biochemical Journal Biochemical Journal, Portland Press, 2004, 377, pp.569-578 HAL |
| ISSN: | 0264-6021 1470-8728 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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