ADP ribosylation factor like 2 (Arl2) regulates breast tumor aggressivity in immunodeficient mice.
ADP ribosylation factor like 2 (Arl2) regulates breast tumor aggressivity in immunodeficient mice.
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DOI：
10.1371/journal.pone.0007478
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发表时间：
2009-10-15
期刊：
影响因子：
3.7
通讯作者：
Dumontet C
中科院分区：
文献类型：
--
作者：
Beghin A;Belin S;Hage-Sleiman R;Brunet Manquat S;Goddard S;Tabone E;Jordheim LP;Treilleux I;Poupon MF;Diaz JJ;Dumontet C
我们以前曾报道，ADP核糖基化因子2（Arl 2），一个小的GTP酶，内容影响微管动力学和细胞周期分布在乳腺肿瘤细胞，以及磷酸化P53的程度和分布。在这里，我们表明，在两个不同的人乳腺癌模型中，Arl 2含量对乳腺肿瘤细胞的侵袭性在体外和体内都有重大影响。在体外竞争测定中，Arl 2含量降低的细胞显示出降低的接触抑制、增加的克隆形成或簇形成以及相对于对照细胞的增殖优势。这些细胞还在SCID小鼠中引起更大的肿瘤，这种表型可以通过体内施用针对Arl 2的siRNA来模拟。具有增加的Arl 2含量的细胞在体外和体内均显示出降低的侵袭性，具有增强的坏死，并且还发现含有增加的PP 2A磷酸酶活性。新鲜人肿瘤乳腺样品的rt-PCR分析表明，低Arl 2表达与诊断时较大的肿瘤尺寸和较大的淋巴结受累风险相关。这些数据强调了Arl 2（一种小的GTdR）作为乳腺肿瘤细胞侵袭性的重要调节剂的作用，无论是在体外还是在体内。
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.
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DOI：
10.1083/jcb.149.5.1087
发表时间：
2000-05-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bhamidipati A;Lewis SA;Cowan NJ
通讯作者：
Cowan NJ
影响因子：
50.3
作者：
Neviani, P;Santhanam, R;Perrotti, D
通讯作者：
Perrotti, D
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
3.7
作者：
Behin, Anne;Honore, Stephane;Dumontet, Charles
通讯作者：
Dumontet, Charles
影响因子：
9.2
作者：
Minshull, J;Straight, A;Murray, AW
通讯作者：
Murray, AW