Fig. 4.

Ras/Raf/MEK/ERK and mTOR signaling regulate the growth of Kras; p16p19^null sarcomas and the human RMS cell line RD. (A–C) Proliferation of two stable cell lines established from mouse Kras; p16p19^null RMS tumors of satellite-cell origin (A), of two stable cell lines established from mouse Kras; p16p19^null nonmyogenic sarcomas of Sca1⁺ origin (B), and of the human RMS cell line RD (C) was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in control cultures (dark blue in A and red in B) and after inhibiting mTOR by exposure to 50–100 nMol rapamycin (abbreviated R, light blue in A and orange in B) or to 50–100 nMol torin (abbreviated T) or by inhibiting Ras/Raf/MEK/ERK by exposure to 1–10 μMol U0216 (abbreviated U). (D–G) Mice with Kras; p16p19^null RMS tumors of satellite-cell origin (D and F) or Kras; p16p19^null nonmyogenic sarcomas of Sca1⁺ origin (E and G) were treated daily with rapamycin; treatment prolonged time until killing (P < 0.0001) and impeded growth of both myogenic and nonmyogenic sarcomas.