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.