Differential regulation of the clusterin gene by Ha-ras and c-myc oncogenes and during apoptosis.

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  • Additional Information
    • Source:
      Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0050222 Publication Model: Print Cited Medium: Print ISSN: 0021-9541 (Print) Linking ISSN: 00219541 NLM ISO Abbreviation: J Cell Physiol Subsets: MEDLINE
    • Publication Information:
      Publication: New York, NY : Wiley-Liss
      Original Publication: Philadelphia, Wistar Institute of Anatomy and Biology.
    • Subject Terms:
      Genes, myc* ; Genes, ras* ; Molecular Chaperones*; Apoptosis/*genetics ; Glycoproteins/*genetics ; Proto-Oncogene Proteins c-myc/*physiology ; Proto-Oncogene Proteins p21(ras)/*physiology; Animals ; Apoptosis/radiation effects ; Cell Cycle ; Cell Line, Transformed ; Clusterin ; DNA Fragmentation ; Fibroblasts/metabolism ; Glycoproteins/biosynthesis ; Mutation ; RNA, Messenger/biosynthesis ; Rats ; Recombinant Fusion Proteins/biosynthesis ; Recombinant Fusion Proteins/genetics ; Signal Transduction ; Transfection ; Ultraviolet Rays
    • Abstract:
      Clusterin (ApoJ) is an extracellular glycoprotein expressed during processes of tissue differentiation and regression that involve programmed cell death (apoptosis). Increased clusterin expression has also been found in tumors, however, the mechanism underlying this induction is not known. Apoptotic processes in tumors could be responsible for clusterin gene activation. Alternatively, oncogenic mutations could modulate signal transduction, thereby inducing the gene. We examined the response of the rat clusterin gene to two oncogenes, Ha-ras and c-myc, in transfected Rat1 fibroblasts. While c-myc overexpression did not modify clusterin gene activity, the Ha-ras oncogene produced a seven to tenfold repression of clusterin mRNA; this down-regulation was also observed in the presence of c-myc. Since no induction of the clusterin gene was observed by the two oncogenes, we tested the alternative mechanism involving apoptosis. Growth factor withdrawal induced apoptosis, as shown by DNA degradation and micronuclei formation in the floating cells. Concomittantly we observed a three to tenfold increase in the amount of clusterin mRNA in the adhering cells of Rat1 and the c-myc transformed cell lines, and a weaker induction in the Ha-ras transformed cell line. On the basis of our results, we suggest that clusterin gene induction in the vital cells is produced by signaling molecules that are generated by the apoptotic cells. We conclude that apoptotic processes, not oncogenic mutations, are responsible for increased clusterin expression in tumors.
    • Accession Number:
      0 (Clusterin)
      0 (Glycoproteins)
      0 (Molecular Chaperones)
      0 (Proto-Oncogene Proteins c-myc)
      0 (RNA, Messenger)
      0 (Recombinant Fusion Proteins)
      EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
    • Publication Date:
      Date Created: 19990326 Date Completed: 19990422 Latest Revision: 20061115
    • Publication Date:
      20240829
    • Accession Number:
      10.1002/(SICI)1097-4652(199812)177:4<593::AID-JCP10>3.0.CO;2-F
    • Accession Number:
      10092212