Department of Microbiology, Karolinska Institutet, BOX 280, S-17177 Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19866-71. doi: 10.1073/pnas.0911545106. Epub 2009 Nov 10.
We report that the overexpression of mitochondrial ribosomal protein MRPS18-2 (S18-2) can immortalize primary rat embryonic fibroblasts (REFs). The immortalized cells (18IM) lose contact inhibition, form foci, and are capable of anchorage-independent growth. Concurrently, mesodermal markers, such as vimentin, smooth muscle actin, and Fut4, disappear completely. 18IM cells express embryonic stem cell markers, such as SSEA-1, Sox2, and Oct3/4. In confluent cultures, a portion of cells also express ectoderm- and endoderm-specific pan-keratin, ectoderm-specific beta-III-tubulin, mesoderm-specific MHC class II, and become stainable for fat with Oil red O. None of these changes was detected in c-myc+Ha-ras (MR)-transformed cells. In immunodeficient mice, 18IM cells formed small transiently growing tumors that have down-regulated SSEA-1 and showed pan-keratin staining. We conclude that S18-2 can immortalize REFs and induces them to express stem cell traits.
我们报告称，线粒体核糖体蛋白 MRPS18-2（S18-2）的过表达可以使原代大鼠胚胎成纤维细胞（REFs）永生化。永生化细胞（18IM）失去接触抑制，形成焦点，并能够进行锚定非依赖性生长。同时，中胚层标记物，如波形蛋白、平滑肌肌动蛋白和 Fut4，完全消失。18IM 细胞表达胚胎干细胞标记物，如 SSEA-1、Sox2 和 Oct3/4。在汇合培养物中，一部分细胞还表达外胚层和内胚层特异性的全角蛋白、外胚层特异性的β-III-微管蛋白、中胚层特异性的 MHC Ⅱ类，并可被油红 O 染色为脂肪。在 c-myc+Ha-ras（MR）转化细胞中未检测到这些变化。在免疫缺陷小鼠中，18IM 细胞形成了小的短暂生长的肿瘤，这些肿瘤下调了 SSEA-1 并显示出全角蛋白染色。我们得出结论，S18-2 可以使 REF 永生化，并诱导其表达干细胞特征。
