Constitutive activation of gp130 leads to neuroendocrine differentiation in vitro and in vivo

The Prostate
Jodie PalmerPaul J Hertzog

Abstract

Neuroendocrine (NE) differentiation in prostate tumors has been correlated with androgen independent disease and increased risk of death. In vitro, IL-6 initiates NE differentiation utilizing the signal transduction initiated by the interaction with IL-6R alpha and gp130. In this study we analysed the NE differentiation process in vitro and in vivo using the LNCaP androgen dependent cell line via ligand independent induction of NE differentiation. LNCaP cells were transfected with a constitutively active gp130 subunit, gp130act. Cell proliferation rate was determined and clones were examined for neuroendocrine differentiation by morphological change, upregulation of CgA and serotonin and formation of dense core vesicles with LNCaP parental cells as the control. Xenograft formation was examined and compared in immunocompromised mice. Gp130act expression promoted significant neuroendocrine differentiation in vitro as determined by a NE like morphology change (increased neurite like extension formation), elevated CgA expression and the formation of dense core vesicles (DCV). These measures concurred with those examined in LNCaP cells following 100 ng/ml IL-6 treatment. Further investigation of the LNCaP gp130act cells in vivo, in ...Continue Reading

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Citations

Jun 3, 2006·Medical Microbiology and Immunology·Jürgen Scheller, Stefan Rose-John
Jun 2, 2007·World Journal of Urology·Bernard PauleAlexandre de la Taille
Sep 29, 2011·The Journal of Urology·Lisa LaskiewiczLucia R Languino
Sep 2, 2006·Critical Reviews in Oncology/hematology·H G van der Poel
Nov 21, 2007·Urologia Internationalis·Luca CindoloAlexandre de la Taille
Jul 13, 2016·The Prostate·Andrew FarachGustavo E Ayala
Sep 21, 2005·The Prostate·Christian G SauerRainer Grobholz

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