Immortalization of human cells by mutant and chimeric primate polyomavirus T-antigen genes

Frank J. O'Neill, Richard J. Frisque, Xiaoling Xu, Yao Xiong Hu, Helen Carney

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Abstract

Human fibroblasts were morphologically transformed with wild type and mutant SV40 T-antigens (T-Ags) and with SV40/JCV and SV40/BKV chimeric T-Ags. The transformants were then assayed for the attainment of immortal cell growth. Several observations relating T-Ag and T-Ag domains to immortalization were made. Approximately 10% of SV40-transformants became immortal. Transformants generated by transfection or infection of cells with C-terminal T-Ag deletion mutants of SV40 did not immortalize. SV40/JCV and SV40/ BKV chimeric T-Ags, containing C-terminal sequences from JCV or BKV, immortalized cells more efficiently than did the intact SV40 T-Ag, suggesting that the C-termini of the JCV and BKV T-Ags contain an enhanced immortalization function. However, chimeras in which the N-terminal or proximal-central portions of T-Ag were composed of JCV sequences failed to immortalize but did induce transformation. Constructs in which the JCV T-Ag Rb binding domain was replaced with SV40 sequences transformed human cells, but again the cells failed to immortalize. Transformants and immortalized cell lines produced by some SV40/JCV chimeras, contained p53 which was unbound by T-Ag. This occurred under conditions where p53 from SV40 and SV40/BKV transformants was bound to T-Ag. This may reflect the reduced stability of the SV40/JCV T-Ags.

Original languageEnglish (US)
Pages (from-to)1130-1139
Number of pages10
JournalOncogene
Volume10
Issue number6
StatePublished - Mar 16 1995

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Genetics
  • Molecular Biology

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    O'Neill, F. J., Frisque, R. J., Xu, X., Hu, Y. X., & Carney, H. (1995). Immortalization of human cells by mutant and chimeric primate polyomavirus T-antigen genes. Oncogene, 10(6), 1130-1139.