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

被引：41

作者：

Shimada, H

Liu, TL

Ochiai, T

Shimizu, T

Haupt, Y

Hamada, H

Abe, T

Oka, M

Takiguchi, M

Hiwasa, T

机构：

[1] Chiba Univ, Grad Sch Med, Dept Biochem & Genet, Chuo Ku, Chiba 2608670, Japan

[2] Chiba Univ, Grad Sch Med, Acad Dept Surg, Chuo Ku, Chiba 2608670, Japan

[3] Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel

[4] Sapporo Med Univ, Dept Mol Med, Chuo Ku, Sapporo, Hokkaido 0608556, Japan

[5] Yamaguchi Univ, Sch Med, Dept Surg 2, Yamaguchi 7558505, Japan

来源：

ONCOGENE | 2002年 / 21卷 / 08期

关键词：

p33(ING1); p53; gene therapy; esophageal cancer; Mdm2;

D O I：

10.1038/sj.onc.1205176

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To investigate the effect of p33(ING1) on wild-type p53 gene therapy, T.Tn human esophageal carcinoma cells were stably transfected with p33(ING1) cDNA. Infection with Adp53 (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 tine. 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.

引用

页码：1208 / 1216

页数：9

共 71 条

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