Enhanced expression of the proto-oncogenes fos and raf in the rhabdomyosarcoma cell line BA-HAN-1C after differentiation induction with retinoic acid and N-methylformamide
Corresponding Author
N. E. Gabbert
Institute of Pathology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Dept. of Pathology, Johannes Gutenberg University of Mainz, Langenbeckstr. 1, D-6500 Mainz, FRGSearch for more papers by this authorC.- D. Gerharz
Institute of Pathology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorU. Ramp
Institute of Pathology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorJ. Hoffmann
Institute of Pathology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorO. Oster
Department of Internal Medicine, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorF. Oesch
Institute of Toxicology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorJ. Doehmer
Institute of Toxicology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorCorresponding Author
N. E. Gabbert
Institute of Pathology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Dept. of Pathology, Johannes Gutenberg University of Mainz, Langenbeckstr. 1, D-6500 Mainz, FRGSearch for more papers by this authorC.- D. Gerharz
Institute of Pathology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorU. Ramp
Institute of Pathology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorJ. Hoffmann
Institute of Pathology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorO. Oster
Department of Internal Medicine, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorF. Oesch
Institute of Toxicology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorJ. Doehmer
Institute of Toxicology, Johannes Gutenberg-University of Mainz, D-6500 Mainz, FRG
Search for more papers by this authorAbstract
BA-HAN-1C is a clonal rat rhabdomyosarcoma cell line consisting of proliferating mononuclear tumor cells, some of which spontaneously fuse to form terminally differentiated post-mitotic myotubes. Exposure of BA-HAN-1C cells to retinoic acid (RA) or N-methylformamide (NMF) resulted in a significant inhibition of proliferation (p < 0.001) and in cellular differentiation, as evidenced by a significant increase in the creatine kinase (CK) activity (p < 0.05) and the number of terminally differentiated post-mitotic myotubes (p < 0.001). Furthermore, between 5% (NMF) and 30% (RA) of the mononuclear tumor cells exhibited ultrastructural features of rhabdomyogenic differentiation, not observed in their mononuclear counterparts under standard growth conditions. Although BA-HAN-1C cells responded to both inducers of differentiation, differences in time course and magnitude of both increase of differentiation and growth inhibition were observed. These effects of RA and NMF were preceded by a marked enhancement of c-raf expression which became evident 6 and 12 hr after exposure to RA and NMF, respectively, and which persisted throughout the observation period of 5 days. Furthermore, a transient expression of c-fos could be observed 15 and 30 min after exposure to RA. Our results suggest that c-raf expression might be implicated in the differentiation process of BA-HAN-1C tumor cells.
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