title: ADP ribosylation factor like 2 (Arl2) regulates breast tumor aggressivity in immunodeficient mice.
abstract: We have previously reported that ADP ribosylation factor like 2 (Arl2), a small GTPase, content influences microtubule dynamics and cell cycle distribution in breast tumor cells, as well as the degree and distribution of phosphorylated P53. Here we show, in two different human breast adenocarcinoma models, that Arl2 content has a major impact on breast tumor cell aggressivity both in vitro and in vivo. Cells with reduced content of Arl2 displayed reduced contact inhibition, increased clonogenic or cluster formation as well as a proliferative advantage over control cells in an in vitro competition assay. These cells also caused larger tumors in SCID mice, a phenotype which was mimicked by the in vivo administration of siRNA directed against Arl2. Cells with increased Arl2 content displayed reduced aggressivity, both in vitro and in vivo, with enhanced necrosis and were also found to contain increased PP2A phosphatase activity. A rt-PCR analysis of fresh human tumor breast samples suggested that low Arl2 expression was associated with larger tumor size and greater risk of lymph node involvement at diagnosis. These data underline the role of Arl2, a small GTPase, as an important regulator of breast tumor cell aggressivity, both in vitro and in vivo.
authors.affiliation: INSERM U590, Université Lyon 1, ISPB, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Beghin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Belin
authors.forename: Rouba
authors.initials: R
authors.lastname: Hage-Sleiman
authors.forename: Rouba
authors.initials: R
authors.lastname: Hage Sleiman
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Brunet Manquat
authors.forename: Sophie
authors.initials: S
authors.lastname: Goddard
authors.forename: Eric
authors.initials: E
authors.lastname: Tabone
authors.forename: Lars P
authors.initials: LP
authors.lastname: Jordheim
authors.forename: Isabelle
authors.initials: I
authors.lastname: Treilleux
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Poupon
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Diaz
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D054648:Protein Phosphatase 2; C485819:Arl2 protein, mouse; D019204:GTP-Binding Proteins