Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells.
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.
Molecular Biology Research Program, Case Western Reserve University, Henry Ford Health Sciences Center, Detroit, Michigan 48202.
S O
SO
Freytag
D L
DL
Paielli
J D
JD
Gilbert
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011347:Procollagen / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011347:Procollagen; D012333:RNA, Messenger; D015500:Chloramphenicol O-Acetyltransferase