Expression of cell cycle regulator cdk2ap1 suppresses tumor cell phenotype by non-cell-autonomous mechanisms.

Expression of cell cycle regulator cdk2ap1 suppresses tumor cell phenotype by non-cell-autonomous mechanisms.
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DOI:
10.1016/j.oraloncology.2009.05.001
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发表时间:
2009-09
期刊:
影响因子:
4.8
通讯作者:
Figueiredo, Marxa L.
Figueiredo, Marxa L.
中科院分区:
医学2区
文献类型:
--
作者:
Zolochevska, Olga;Figueiredo, Marxa L.

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我们评估了在上皮细胞或基质细胞中表达细胞周期调节因子cdk 2ap 1在体外和体内减少SCC生长的作用。细胞自主和/或非细胞自主表达的cdk 2ap 1减少肿瘤生长和侵袭和改变细胞周期,粘附,侵袭,血管生成,和凋亡基因的表达,如通过几个体外表型测定,定量真实的时间PCR,并在体内分子成像使用一种新的三向异种移植动物模型进行评估。我们的研究结果表明,促进异常生长的癌细胞和成纤维细胞之间的相互作用可以通过表达cdk 2ap 1最小化,支持一个新的概念,即肿瘤/生长抑制基因可以影响肿瘤发生表型的非细胞自主相互作用的肿瘤微环境。
We evaluated the effect of expressing the cell cycle regulator cdk2ap1 in epithelial or stromal cell compartments to reduce SCC growth in vitro and in vivo. Cell autonomous and/or non-cell autonomous expression of cdk2ap1 reduced tumor growth and invasion and altered cell cycle, adhesion, invasion, angiogenesis, and apoptotic gene expression, as assessed by several in vitro phenotype assays, quantitative real time PCR, and in vivo molecular imaging using a novel three-way xenograft animal model. Our findings suggest that the interactions between cancer cells and fibroblasts that promote abnormal growth can be minimized by expressing cdk2ap1, supporting a novel concept by which tumor/growth suppressor genes can impact tumorigenesis phenotypes from non-cell autonomous interactions within the tumor microenvironment.
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