title: Interleukin 1 alpha mediated inhibition of myogenic terminal differentiation: increased sensitivity of Ha-ras transformed cultures.
abstract: The commitment of myogenically determined cells to terminal differentiation can be modulated by a variety of agents, including growth factors and activated oncogenes. We have examined the effect of interleukin 1 alpha (IL-1 alpha) on the terminal differentiation of a normal myogenically determined cell line and two myogenically determined, differentiation competent cell lines which contain either one or six copies of the activated c-Ha-ras oncogene. Treatment of all cell lines with IL-1 alpha decreased but did not totally inhibit terminal myogenic differentiation. Over the range of IL-1 alpha concentrations assayed (1-40 ng/ml), the c-Ha-ras transformed cell lines demonstrated a significantly greater sensitivity to the inhibitory effects of IL-1 alpha. The inhibition of differentiation was not the result of enhanced proliferation. Interestingly, transformation with activated c-Ha-ras resulted in a decrease in IL-1 alpha receptor number and affinity. The enhanced IL-1 alpha responsiveness of the ras transformants was not the result of increased proliferation or changes in either ras gene expression or protein kinase C activity. IL-1 alpha treatment decreased the steady-state levels of both MyoD1 and myogenin transcripts in the c-Ha-ras transformed but not the normal myogenic cell line. Further studies are required to determine the mechanism(s) responsible for the increased sensitivity of the c-Ha-ras transformed cultures to the inhibitory effects of IL-1 alpha.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5121.
authors.forename: M A
authors.initials: MA
authors.lastname: Harrington
authors.forename: R
authors.initials: R
authors.lastname: Daub
authors.forename: A
authors.initials: A
authors.lastname: Song
authors.forename: J
authors.initials: J
authors.lastname: Stasek
authors.forename: J G
authors.initials: JG
authors.lastname: Garcia
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D003864:Depression, Chemical; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D009124:Muscle Proteins / Q000096:biosynthesis; D009132:Muscles / Q000166:cytology*; D017570:MyoD Protein; D018008:Myogenin; D009687:Nuclear Proteins / Q000096:biosynthesis; D010750:Phosphoproteins / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000199:Actins; D007375:Interleukin-1; D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D018008:Myogenin; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011493:Protein Kinase C; D016283:Proto-Oncogene Proteins p21(ras); D013755:Tetradecanoylphorbol Acetate