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An unusual H-Ras mutant isolated from a human multiple myeloma line leads to transformation and factor-independent cell growth.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print Cited Medium: Print ISSN: 0950-9232 (Print) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE
    • بيانات النشر:
      Publication: <2002->: Basingstoke : Nature Publishing Group
      Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-
    • الموضوع:
      Genes, ras*/physiology ; Mutation*; Cell Transformation, Neoplastic/*genetics ; Multiple Myeloma/*genetics; Animals ; Cell Division/genetics ; Cell Division/physiology ; Growth Substances/physiology ; Guanosine Triphosphate/metabolism ; Humans ; Mice ; Tumor Cells, Cultured
    • نبذة مختصرة :
      Multiple myeloma (MM) is an incurable plasma cell malignancy. To investigate biochemical lesions associated with MM, we constructed an expression cDNA library from the OPM-2 human myeloma line. A highly transforming H-Ras mutant was identified by transfection analysis using NIH 3T3 cells. DNA sequencing demonstrated a single-point mutation at position 117 located in the guanine nucleotide-binding site resulting in a lysine-to-glutamic acid substitution. This mutant, H-Ras (K117E), was found to be constitutively activated in terms of GTP binding. We compared the biological effects of H-Ras (K117E) and H-Ras (G12V) in 32D murine hematopoietic progenitor cells. Whereas both Ras proteins are constitutively activated, 32D cells expressing H-Ras (G12V) are still dependent on IL-3 for survival and proliferation while cells carrying H-Ras (K117E) become IL-3 independent. Similar experiments conducted with the B9 line, an IL-6-dependent hybridoma, also demonstrated that B9/H-Ras (K117E) became IL-6-independent. Expression of H-Ras (K117E) in the human IL-6-dependent ANBL-6 myeloma line resulted in enhanced proliferation at suboptimal concentrations of IL-6. These observations suggest that H-Ras mutations at the binding site for the GTP nucleotide ring structure may also represent activating lesions and have additional biological effects when compared to previously described Ras mutants.
    • الرقم المعرف:
      0 (Growth Substances)
      86-01-1 (Guanosine Triphosphate)
    • الموضوع:
      Date Created: 20030206 Date Completed: 20030228 Latest Revision: 20041117
    • الموضوع:
      20240627
    • الرقم المعرف:
      10.1038/sj.onc.1206180
    • الرقم المعرف:
      12569357