ECTOPIC EXPRESSION OF THE CCAAT ENHANCER-BINDING PROTEIN-ALPHA PROMOTES THE ADIPOGENIC PROGRAM IN A VARIETY OF MOUSE FIBROBLASTIC CELLS

ECTOPIC EXPRESSION OF THE CCAAT ENHANCER-BINDING PROTEIN-ALPHA PROMOTES THE ADIPOGENIC PROGRAM IN A VARIETY OF MOUSE FIBROBLASTIC CELLS
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DOI:
10.1101/gad.8.14.1654
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发表时间:
1994-07-15
影响因子:
10.5
通讯作者:
GILBERT, JD
GILBERT, JD
中科院分区:
生物学1区
文献类型:
--
作者:
FREYTAG, SO;PAIELLI, DL;GILBERT, JD

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CCAAT/增强子结合蛋白 α (C/EBP α) 参与脂肪细胞分化的调节。在这项研究中,我们研究了 C/EBP α 促进多种成纤维细胞脂肪生成程序的潜力。通过逆转录病毒和 DNA 转染将 C/EBP α 基因转导至八种小鼠成纤维细胞系中,以不同的频率产生脂肪细胞集落。最显着的结果是用 NIH-3T3 细胞获得的,其中当 C/EBP α 基因被逆转录病毒转导时,表现出脂肪细胞形态的 G418 抗性集落的百分比可重复地 >50%。促进脂肪生成程序的能力需要 C/EBP α 的有效转录激活结构域,而 C/EBP β 则没有观察到这种能力。矛盾的是,尽管它具有抗有丝分裂作用,但稳定表达大量 C/EBP α 的克隆细胞系却很容易产生。 BALB/c-3T3 细胞中 C/EBP α 的稳定表达可显着增强其最终分化为脂肪细胞的能力。结果表明,C/EBP α 可以有效促进多种小鼠成纤维细胞的脂肪形成程序,包括那些很少或没有自发脂肪形成能力的细胞。
The CCAAT/enhancer-binding protein alpha (C/EBP alpha) has been implicated in the regulation of adipoblast differentiation. In this study we investigate the potential of C/EBP alpha to promote the adipogenic program in a variety of fibroblastic cells. Transduction of the C/EBP alpha gene into eight mouse fibroblastic cell lines by retroviruses and DNA transfection generates adipocyte colonies at variable frequencies. The most dramatic results are obtained with NIH-3T3 cells, in which the percentage of G418-resistant colonies that exhibit the adipocyte morphology is reproducibly >50% when the C/EBP alpha gene is transduced by retroviruses. The ability to promote the adipogenic program requires the potent transcriptional activation domain of C/EBP alpha and is not observed with C/EBP beta. Paradoxically, in spite of its antimitogenic effects, clonal cell lines that stably express high amounts of C/EBP alpha can readily be generated. Stable expression of C/EBP alpha in BALB/c-3T3 cells dramatically enhances their ability to terminally differentiate into adipocytes. The results demonstrate that C/EBP alpha can efficiently promote the adipogenic program in a variety of mouse fibroblastic cells, including those that have little or no spontaneous capacity to undergo adipogenesis.