Nwokafor Chiso U, Sellers Rani S, Singer Robert H
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
Oncotarget. 2016 Nov 8;7(45):72662-72671. doi: 10.18632/oncotarget.12083.
Cells that are able to localize β-actin mRNA efficiently have decreased metastatic potential. Invasive carcinoma cells derived from primary mammary tumors have reduced levels of an RNA binding protein IMP1/ZBP1/IGF2BP1, required for β-actin mRNA localization. We showed previously that in human breast carcinoma cells in vitro, this protein suppresses invasion. In this work we examined whether its re-expression can suppress breast cancer metastasis in a breast cancer mouse model. We developed a mouse conditionally expressing IMP1-GFP (hereinafter referred to as the IMP1 transgene) specifically in the mammary gland of a PYMT breast cancer mouse. We found that mice conditionally expressing the IMP1 transgene showed little or no metastases to the lungs from the primary tumor in contrast to PYMT mice not expressing IMP1, which uniformly develop metastases at an early stage.
能够有效定位β-肌动蛋白mRNA的细胞具有降低的转移潜能。源自原发性乳腺肿瘤的侵袭性癌细胞中,β-肌动蛋白mRNA定位所需的RNA结合蛋白IMP1/ZBP1/IGF2BP1水平降低。我们之前表明,在体外人乳腺癌细胞中,这种蛋白会抑制侵袭。在这项研究中,我们检测了其重新表达是否能在乳腺癌小鼠模型中抑制乳腺癌转移。我们构建了一种在PYMT乳腺癌小鼠乳腺中特异性条件性表达IMP1-GFP(以下简称IMP1转基因)的小鼠。我们发现,与未表达IMP1且早期均会发生转移的PYMT小鼠相比,条件性表达IMP1转基因的小鼠原发性肿瘤向肺部的转移很少或没有。