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Publication : Growth factor responsiveness: role of MyoD and myogenin.

First Author  Wolf JR Year  1992
Journal  Exp Cell Res Volume  202
Issue  1 Pages  105-12
PubMed ID  1324843 Mgi Jnum  J:2187
Mgi Id  MGI:50711 Doi  10.1016/0014-4827(92)90409-2
Citation  Wolf JR, et al. (1992) Growth factor responsiveness: role of MyoD and myogenin. Exp Cell Res 202(1):105-12
abstractText  A differentiation-defective variant (DD-1) of the MM14 myoblasts acquired the ability to synthesize DNA in response to treatment with epidermal growth factor (EGF) (R. W. Lim and S. D. Hauschka, 1984, Dev. Biol. 105, 48) and no longer expressed myogenic determinant genes (i.e., MyoD and myogenin) (P.R. Mueller, and B. Wold, 1989, Science 246, 780). To determine the effect of expression of MyoD on EGF responsiveness, DD-1 cells were cotransfected with a MyoD expression vector and with pRSVneo. A clone, MyoDD-1 cells, which was G418 resistant, formed multinuclear syncitia, and also expressed MyoD and myogenin, was further characterized. EGF responsiveness, as assessed by DNA synthesis, was decreased 5- to 10-fold in the MyoDD-1 cells from that in G418-resistant control DD-1 cells, despite similar EGF receptor numbers and binding affinities of the receptors. Responsiveness of MyoDD-1 cells to fibroblast growth factor (FGF) was also diminished although to a lesser extent. To determine the effects of decreased myogenic determinant gene expression on mitogen responsiveness, MM14 myoblasts were grown in medium supplemented with 5 microM 5-bromo-2'-deoxyuridine (BUdR-MM14). BUdR-MM14 cells had decreased expression of MyoD and myogenin, did not fuse, and had an altered morphology, from round to flat. The BUdR effect on fusion and cell shape was reversed by growth in control medium. BUdR-MM14 cells were responsive to EGF and had enhanced responsiveness to FGF. The combined studies support the view that expression of MyoD and/or myogenin contributes to negative regulation of mitogen responsiveness.
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