Abolishment of c-fos inducibility in ras-transformed mouse osteoblast cell lines.
Proto-oncogene c-fos is induced by many types of cellular stimuli, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), epidermal growth factor (EGF), serum (fetal bovine), calcium ionophore A23187, and dibutyryl cAMP (But2cAMP). In this study, c-fos induction was abolished in ras-transformed mouse osteoblast cells (MC3T3). Transformants of MC3T3 were isolated after transfection with Ki or Ha murine sarcoma virus DNA. All Ki- or Ha-ras transformed MC3T3 clones examined showed exceedingly low levels of c-fos induction by all inducers, as determined by the change in amounts of c-fos mRNA or its product. Induction of other TPA-responsive genes, such as metallothionein, was not altered in some ras-transformed cells; c-myc and c-jun expression was constitutively high in all the ras-transformed clones. Nuclear extracts and gel shift assay showed that the binding activity to c-fos enhancer element (serum response element) was altered in ras-transformed cells. These results indicate that transformation with ras oncogene induces modification of c-fos enhancer binding factors and that this modification is one cause for the decrease in c-fos induction.
Nose
K
K
Department of Cancer Cell Research, University of Tokyo, Japan.
Itami
M
M
Satake
M
M
Ito
Y
Y
Kuroki
T
T
D000818:Animals; D002461:Cell Line, Transformed; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos; D012313:RNA / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate; D014157:Transcription Factors / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D012313:RNA; D013755:Tetradecanoylphorbol Acetate