Both p53-PUMA/NOXA-Bax-mitochondrion and p53-p21cip1 pathways are involved in the CDglyTK-mediated tumor cell suppression.
CDglyTK fusion suicide gene has been well characterized to effectively kill tumor cells. However, the exact mechanism and downstream target genes are not fully understood. In our study, we found that CDglyTK/prodrug treatment works more efficiently in p53 wild-type (HONE1) cells than in p53 mutant (CNE1) cells. We then used adenovirus-mediated gene delivery system to either knockdown or overexpress p53 and its target genes in these cells. Consistent results showed that both p53-PUMA/NOXA/Bcl2-Bax and p53-p21 pathways contribute to the CDglyTK induced tumor cell suppression. Our work for the first time addressed the role of p53 related genes in the CDglyTK/prodrug system.
Yu
Zhendong
Z
Department of Clinical laboratory, Peking University Shenzhen Hospital, Guangdong, China. zdyu@hotmail.com
Wang
Hao
H
Zhang
Libin
L
Tang
Aifa
A
Zhai
Qinna
Q
Wen
Jianxiang
J
Yao
Li
L
Li
Pengfei
P
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy*; D011355:Prodrugs / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013937:Thymidine Kinase / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C498702:PMAIP1 protein, human; D011355:Prodrugs; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D013937:Thymidine Kinase