Increased Hepatic Cell Proliferation and Lung Abnormalities in Mice Deficient in CCAAT/Enhancer Binding Protein α

Flodby, Per; Barlow, Carrolee; Kylefjord, Helen; Ährlund‐Richter, Lars; Xanthopoulos, Kleanthis G.

doi:10.1074/jbc.271.40.24753

Cited by 272 publications

(253 citation statements)

References 59 publications

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“…Since only 88 of the 164 tumors analyzed contained data regarding histological differentiation, it is possible that in a larger sample a significant association would emerge. A correlation of C/EBPα expression with differentiation is supported by its role on airway epithelial differentiation as demonstrated by our group and others (27)(28)(29)(30), and had been seen in our initial C/EBPα study in lung cancer (29).…”

Section: Discussionsupporting

confidence: 71%

“…In addition, hyperproliferation and differentiation arrest of type II pneumocytes were seen in a C/EBPα knockout mice model (27) as well as in the lung-specific conditional mouse model of C/EBPα deletion developed by our group (28). In fact, the prominent lung phenotype of our conditional mouse model resulted in respiratory arrest and death (28).…”

Section: Discussionmentioning

confidence: 66%

“…Abnormal proliferation of type II pneumocytes is seen in the context of the lethal phenotype of C/EBPα −/− knockout mice (27). In the lung-specific conditional C/ EBPα knockout mouse developed by our group, a block in type II cell differentiation and increase in respiratory epithelial proliferation is seen (28).…”

Section: Introductionmentioning

confidence: 91%

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Immunohistochemical analysis of C/EBPα in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors: A correlative study of E3590

Costa

Kocher

et al. 2007

Lung Cancer

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 66%

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Immunohistochemical analysis of C/EBPα in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors: A correlative study of E3590

Costa

Kocher

et al. 2007

Lung Cancer

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“…It has also been reported that the C/EBPalphamediated myoblast to adipocyte transition of C2C12 takes place in the absence of adipocyte differentiation medium (Fux et al, 2004). C/EBPbeta and C/EBPalpha are also key molecules for myeloid development (Friedman, 2002) or hepatocyte differentiation (Flodby et al, 1996). C/EBPalpha À/À mice lack neutrophils and eosinophils, but retain monocytes, lymphocytes, erythroid cells and immature myeloblasts .…”

Section: Discussionmentioning

confidence: 93%

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

et al. 2006

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Fms interacting protein (FMIP) is a substrate for Fms tyrosine kinase, and a nuclear/cytoplasm shuttling protein with a leucine zipper. As the phosphorylation of FMIP is observed in insulin-stimulated preadipocytes, we examined the role of FMIP in adipocyte differentiation, using the mesenchymal multipotent stem cells, C2C12 cells, that can differentiate into adipocytes, muscle cells and osteoblasts. Ectopic expression of FMIP in C2C12 impairs the adipocyte differentiation induced by treatment with insulin, dexamethasone and 3-isobutyl-1-methylxanthine. These cells exhibit muscle phenotype with multinuclear morphology. Furthermore, knockdown of endogenous FMIP expression by small interfering RNA improves adipocytic lineage commitment of C2C12 cells, while impairing muscle differentiation. Upon stimulation with insulin, CCAAT/enhancer binding protein (C/EBP)-beta, but not C/EBPalpha, is upregulated in cells expressing ectopic FMIP, whereas in FMIP knockdown cells, C/EBPalpha is constitutively expressed. Ectopic expression of C/EBPalpha counteracts the effects of FMIP, whereas C/EBPalpha knockdown partially mimics the effects of FMIP in this system. Northern blot analysis and reverse transcriptase-polymerase chain reaction study reveal that ectopic FMIP-expressing cells do not contain the polyadenylated C/EBPalpha mRNA, but contain the C/EBPalpha pre-mRNA, suggesting that FMIP plays a role in RNA processing and/or export. Indeed, a member of the THO complex that plays a role in mRNA export, THOC1, is co-precipitated with FMIP. The data we have acquired on FMIP suggest that it is a target for tyrosine kinase receptors that potentiate mRNA export.

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“…Expression of antisense C/EBPα RNA prevents both growth arrest and terminal differentiation of 3T3-L1 adipocytes [18]. In addition, C/EBPα is critical in regulating the differentiation of preadipocytes, myeloid cells, hepatocytes and pneumocytes [3,5,[19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

C/EBPαp30 plays transcriptional regulatory roles distinct from C/EBPαp42

et al. 2007

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CCAAT/enhancer binding protein α (C/EBPα) is a transcriptional regulatory factor that inhibits cell proliferation, and alternative translational initiation produces two polypeptides, C/EBPαp30 and C/EBPαp42. By expression profiling, it was revealed that C/EBPαp30 specifically inhibited a unique set of genes, including MPP11, p84N5 and SMYD2, which were not affected by C/EBPαp42 in both QSG-7701 hepatocyte cell line and QGY-7703 hepatoma cells. Semiquantitative RT-PCR analysis independently confirmed these results. Chromatin immunoprecipitation assay showed that C/EBPαp30 bound to the promoters of these genes more strongly than C/EBPαp42. In clinical hepatoma samples in which C/EBPα was downregulated, all three genes specifically inhibited by C/EBPαp30 were upregulated. However, repression of MPP11, p84N5 and SMYD2 genes might not be directly involved in C/EBPαp30-mediated growth inhibition. Our data suggest that C/EBPαp30 regulates a unique set of target genes and is more than a dominant-negative regulator of C/EBPαp42.

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Increased Hepatic Cell Proliferation and Lung Abnormalities in Mice Deficient in CCAAT/Enhancer Binding Protein α

Cited by 272 publications

References 59 publications

Immunohistochemical analysis of C/EBPα in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors: A correlative study of E3590

Immunohistochemical analysis of C/EBPα in non-small cell lung cancer reveals frequent down-regulation in stage II and IIIA tumors: A correlative study of E3590

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBPalpha

C/EBPαp30 plays transcriptional regulatory roles distinct from C/EBPαp42

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