Su Su

Publications (1)2.48 Total impact

• Source

  Available from: Motoko Yamamoto

  Article: Mutations in p53 cDNA sequence introduced by retroviral vector.

  Su Su, Atsushi Watanabe, Motoko Yamamoto, Eiitsu Nakajima, Koichi Miyake, Takashi Shimada
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  ABSTRACT: The high mutation rates of retroviruses are a potential problem with retroviral vectors. We studied the mutation rates and spectra of p53 sequences transduced with a retroviral vector in a cancer gene therapy model. When p53-deficient H358 non-small cell lung cancer cells were treated with a retroviral vector carrying normal p53 cDNA, most of transduced cells were killed by apoptosis. However, a small number of clones escaped p53-mediated apoptosis. We examined the p53 cDNA structure in these resistant clones. PCR-based analysis showed that 88/102 clones had detectable mutations in p53, including gross rearrangements, deletions/insertions, and base substitutions. To study the mutation rate of the p53 sequence in all transduced clones, the retroviral vector containing the non-functional p53 gene and the Neo-resistant marker gene was introduced into H358 cells. Only one of 95 isolated clones showed a base substitution. These results indicate that the mutation rate of p53 is not particularly high, but there is a significant risk that cancer cells will resist p53 gene therapy as a result of retroviral replication errors.
  Biochemical and Biophysical Research Communications 03/2006; 340(2):567-72. · 2.48 Impact Factor