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  • Original Paper
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Facilitation of adenoviral wild-type p53-induced apoptotic cell death by overexpression of p33ING1 in T.Tn human esophageal carcinoma cells

Oncogene volume 21, pages 1208–1216 (2002)Cite this article

Abstract

To investigate the effect of p33ING1 on wild-type p53 gene therapy, T.Tn human esophageal carcinoma cells were stably transfected with p33ING1 cDNA. Infection with Ad-p53 (recombinant adenovirus containing wild-type p53) into p33-transfected cells reduced cell viability, while infection with empty vector had little effect. This reduced viability was shown to be due to apoptotic cell death by the TUNEL (terminal deoxynucleotidyl transferase-mediated nick end-labeling) assay. Following infection with Ad-p53, levels of p53 were similar in p33-expressing cells and in the parental line. However, levels of p21 and Mdm2 were elevated in p33-transfected cells. Nonetheless, this enhanced expression of Mdm2 appeared to be ineffective in downregulating p53. Transient transfection with mutant Mdm2 prior to Ad-p53 infection provided a significant protection as compared with cells transfected with wild-type Mdm2. These results imply a synergistic effect between p33 and p53 in the induction of apoptosis of human esophageal carcinoma cells. A role for Mdm2 in this synergism is suggested.

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Abbreviations

wtp53:

wild type p53

Ad-p53:

recombinant wild-type p53 adenoviral vector

Ad-LZ:

recombinant LacZ adenoviral vector

CMV:

cytomegalovirus

MOI:

multiplicity of infection

MTT:

3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide

PBS:

phosphate-buffered saline

TUNEL:

terminal deoxynucleotidyl transferase-mediated nick end-labeling

BaP:

benzo[a]pyrene

ALLN:

acetyl-Leu-Leu-norleucinal

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Acknowledgements

The authors thank Dr Toshiyoshi Fujiwara (Okayama University Medical School) for providing us with adenoviral vectors and also for excellent advice on preparation of the vectors. This work was partly supported by an Advanced Medicine Development Project from the Ministry of Education, Science, Sports and Culture of Japan.

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Author notes

  1. Hideaki Shimada and Tian-Ling Liu: H Shimada and T-L Liu contributed equally to this work

Authors and Affiliations

  1. Department of Academic Surgery, Chiba University, Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan

    Hideaki Shimada, Tian-Ling Liu, Takenori Ochiai & Takanori Shimizu

  2. Department of Biochemistry and Genetics, Chiba University, Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan

    Masaki Takiguchi & Takaki Hiwasa

  3. Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem, 91120, Israel

    Ygal Haupt

  4. Department of Molecular Medicine, Sapporo Medical University, S1 W17, Chuo-ku, Sapporo, 060-8556, Japan

    Hirofumi Hamada

  5. Department of Surgery II, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan

    Toshihiro Abe & Masaaki Oka

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  1. Hideaki Shimada
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Correspondence to Takaki Hiwasa.

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Shimada, H., Liu, TL., Ochiai, T. et al. Facilitation of adenoviral wild-type p53-induced apoptotic cell death by overexpression of p33ING1 in T.Tn human esophageal carcinoma cells. Oncogene 21, 1208–1216 (2002). https://doi.org/10.1038/sj.onc.1205176

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