ERK1/2 pathway : an integrating node of converging signaling pathways in normal prostate epithelial cells.
type: Distribution
access URL: https://theses.hal.science/tel-00824334
format: HTML
issued: 2026-05-11T02:03:36.760653
modified: 2026-05-11T02:03:36.693247

test_moissonnage_selune
type: Agent

ERK1/2 pathway : an integrating node of converging signaling pathways in normal prostate epithelial cells.
type: Dataset
contact point: Organization
  fn: CCSD
keyword: non-genomic-signaling
keyword: infoeu-reposemanticsdoctoralthesis
keyword: recepteur-aux-androgenes
keyword: signalisation-non-genomique
keyword: prostate
keyword: voie-erk12
keyword: normal-epithelial-cells
keyword: transactivation
keyword: recepteur-a-legf
keyword: il-6
keyword: egf-receptor
keyword: proliferation
keyword: sdvsalife-sciences-q-bioagricultural-sciences
keyword: cellules-epitheliales-normales
keyword: androgen-receptor
keyword: erk12-pathway
keyword: theses
landing page: https://theses.hal.science/tel-00824334
description: Prostate development and cell homeostasis involve strict control of androgen and growth factors induced signaling pathways. These signaling pathways are deeply altered in prostate cancer, especially during late stages. In this work, the RWPE-1 immortalized cell line derived from human prostate epithelium has been used to study the signaling pathways regulating cell proliferation and their crosstalk. Optimal RWPE-1 proliferation is dependent on EGF (Epidermal Growth Factor), that also controls normal epithelial development. EGF-R family is also involved in cancer cell proliferation. EGF-dependent RWPE- 1 cell proliferation relies strictly on the ERK1/2 pathway which is then seen as a signal integrating node. Specific inhibitors showed essential role of androgen receptor in EGF mediated ERK1/2 activation. Androgen receptor is associated with several signaling molecules in RWPE-1 cells. I show here for the first time the physical interaction between the androgen receptor and the ERK1/2 activating kinase Raf1. Then, the androgen receptor could directly regulate an essential pathway for epithelial cells proliferation through a non-genomic mechanism. In addition, I showed that IL-6 dependent RWPE-1 cells proliferation requires both ERK1/2 and EGF-R kinase activities, suggesting an IL-6 mediated transactivation of EGF-R. By using several inhibitors, I showed that ADAM (a disintegrin and metalloprotease) family metaloproteases, especialy ADAM17, are involved in this process. IL-6-mediated ADAM proteins activation could lead to the cleavage of a membrane bound EGF-R ligand, leading to ERK1/2 pathway activation. This new mechanism could be involved in the inflammatory situations inducing hyperproliferation of the prostate epithelium, the first step of the transformation process. To conclude, the signaling pathways I studied are strongly connected in normal epithelial cells. The two new mechanisms described in this study lead to ERK1/2 kinases activation, an integrating node o…
identifier: NNT: 2010LYO10292
issued: 2026-05-11T02:03:36.718517
language: fr
modified: 2026-05-11T02:03:36.718522