title: CACNA2D2 promotes tumorigenesis by stimulating cell proliferation and angiogenesis.
abstract: In the present study, we have assessed whether a putative calcium channel α2δ2 auxiliary subunit (CACNA2D2 gene) could be involved in prostate cancer (PCA) progression. We therefore carried out experiments to determine whether this protein is expressed in PCA LNCaP cells and in PCA tissues, and whether its expression may be altered during cancer development. In addition, we evaluated the influence on cell proliferation of overexpressing or downregulating this subunit. In vitro experiments show that α2δ2 subunit overexpression is associated with increased cell proliferation, alterations of calcium homeostasis and the recruitment of a nuclear factor of activated T-cells pathway. Furthermore, we carried out in vivo experiments on immuno-deficient nude mice in order to evaluate the tumorigenic potency of the α2δ2 subunit. We show that α2δ2-overexpressing PCA LNCaP cells are more tumorigenic than control LNCaP cells when injected into nude mice. In addition, gabapentin, a ligand of α2δ2, reduces tumor development in LNCaP xenografts. Finally, we show that the action of α2δ2 on tumor development occurs not only through a stimulation of proliferation, but also through a stimulation of angiogenesis, via an increased secretion of vascular endothelial growth factor in cells overexpressing α2δ2.
authors.affiliation: Laboratoire de Physiologie Cellulaire, INSERM U1003, Villeneuve d'Ascq Cédex, France.
authors.forename: M
authors.initials: M
authors.lastname: Warnier
authors.affiliation: Laboratoire de Physiologie Cellulaire, INSERM U1003, Villeneuve d'Ascq Cédex, France.
authors.forename: M
authors.initials: M
authors.lastname: Roudbaraki
authors.affiliation: Laboratoire de Physiologie Cellulaire, INSERM U1003, Villeneuve d'Ascq Cédex, France.
authors.forename: S
authors.initials: S
authors.lastname: Derouiche
authors.affiliation: Laboratoire de Physiologie Cellulaire, INSERM U1003, Villeneuve d'Ascq Cédex, France.
authors.forename: P
authors.initials: P
authors.lastname: Delcourt
authors.affiliation: Laboratoire de Physiologie Cellulaire, INSERM U1003, Villeneuve d'Ascq Cédex, France.
authors.forename: A
authors.initials: A
authors.lastname: Bokhobza
authors.affiliation: Laboratoire de Physiologie Cellulaire, INSERM U1003, Villeneuve d'Ascq Cédex, France.
authors.forename: N
authors.initials: N
authors.lastname: Prevarskaya
authors.affiliation: Laboratoire de Physiologie Cellulaire, INSERM U1003, Villeneuve d'Ascq Cédex, France.
authors.forename: P
authors.initials: P
authors.lastname: Mariot
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D006706:Homeostasis; D006801:Humans; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000209:etiology*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000209:etiology* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C480968:CACNA2D2 protein, human; D015220:Calcium Channels; D042461:Vascular Endothelial Growth Factor A; D002118:Calcium