ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence.
ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence.
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DOI：
10.1186/1471-2407-11-11
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发表时间：
2011-01-11
期刊：
影响因子：
3.8
通讯作者：
Cerutti JM
中科院分区：
文献类型：
--
作者：
Latini FR;Hemerly JP;Freitas BC;Oler G;Riggins GJ;Cerutti JM
越来越多的证据表明，ABI3 （ABI家族成员3）作为一种肿瘤抑制基因起作用，尽管ABI3的分子机制仍不清楚。本研究研究了ABI3在大量良性和恶性甲状腺肿瘤中的表达，并探讨了ABI3与其潜在伴侣ABI3结合蛋白（ABI3BP）表达之间的相关性。接下来，我们探讨了ABI3在甲状腺和结肠癌细胞系中异位表达的生物学效应，在这些细胞系中，ABI3的表达减少或缺失。我们不仅观察到ABI3在大多数癌症中表达减少或缺失，而且ABI3和ABI3BP表达之间存在正相关。异位表达ABI3足以导致转化活性降低，肿瘤体外生长特性降低，抑制体外非锚定生长和体内肿瘤形成，同时细胞衰老加剧。这些反应伴随着细胞周期抑制剂p21 WAF1的上调和ERK磷酸化和E2F1表达的降低。我们的研究结果将ABI3与一些癌症的发病和进展联系起来，并表明ABI3或其途径可能有兴趣作为治疗靶点。这些结果还表明，ABI3的作用途径应该进一步表征。
Mounting evidence has indicated that ABI3 (ABI family member 3) function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown. The present study investigated ABI3 expression in a large panel of benign and malignant thyroid tumors and explored a correlation between the expression of ABI3 and its potential partner ABI3-binding protein (ABI3BP). We next explored the biological effects of ABI3 ectopic expression in thyroid and colon carcinoma cell lines, in which its expression was reduced or absent. We not only observed that ABI3 expression is reduced or lost in most carcinomas but also that there is a positive correlation between ABI3 and ABI3BP expression. Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased. These responses were accompanied by the up-regulation of the cell cycle inhibitor p21 WAF1 and reduced ERK phosphorylation and E2F1 expression. Our result links ABI3 to the pathogenesis and progression of some cancers and suggests that ABI3 or its pathway might have interest as therapeutic target. These results also suggest that the pathways through which ABI3 works should be further characterized.
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影响因子：
5.4
作者：
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影响因子：
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