Literature DB >> 19550118

Inhibitory effect of wild-type p53 gene on excessive replication of centrosomes in leukemia cell line K562.

Wen-Jun Tian1, Wen-Li Feng, Hong-Bin Wang, Shi-Feng Huang, Wei-Xi Cao, Zong-Gan Huang.   

Abstract

BACKGROUND AND
OBJECTIVE: Mutation and deletion of the p53 gene in tumor cells is one of the major reasons for aneuploid development and genomic instability. Abnormal centrosomes exist in chronic myelogenous leukemia patients at different stages; furthermore, the degree of abnormality is associated with the clinical stage and more severe in the blast crisis stage. This study was to establish the leukemia cell line K562 with the exogenous wild-type p53 (wt-p53) gene, and to explore the effect of the p53 gene on centrosomes in K562 cells.
METHODS: The recombinant adenoviruses carrying the wt-p53 gene (Ad5wtp53), the mutant p53 gene (Ad5mtp53) and the green fluorescent protein gene (Ad5GFP) were amplified respectively in HEK293 cells, and co-infected with cation polybrene into K562 cells respectively; uninfected K562 cells were used as blank control. The infection efficiency was analyzed by flow cytometry. P53 expression was detected by Western blot. Centrosomes were counted under the laser confocal microscope after indirect immunofluorescence staining. The expression of Gadd45a (growth arrest and DNA damage), BubR1 (Bub 1 related) and Aurora A was detected by western blot.
RESULTS: K562 cell line with exogenous wt-p53 gene was established. The infection efficiencies of three groups were over 60%, and P53 sustained expression for 72 h. The percentage of cells with amplified centrosomes (more than 2/cell) in Ad5wtp53 group was decreased to (0.38 +/- 0.02)%, lower than that of blank control group (p < 0.05). Meanwhile, the protein levels of Gadd45a and BubR1 in Ad5wtp53 group were upregulated by 93% and 88% of blank control (p < 0.05), respectively, and the protein level of Aurora A was downregulated by 56% of blank control (p < 0.05).
CONCLUSIONS: P53 protein is sustained to express in K562 cells after being infected by Ad5wtp53. wt-p53 can suppress excessive replication of centrosomes that may contribute to the upregulation of Gadd45a and BubR1 protein expression as well as the downregulation of Aurora A protein expression.

Entities:  

Mesh:

Substances:

Year:  2009        PMID: 19550118

Source DB:  PubMed          Journal:  Ai Zheng


  2 in total

1.  Role of senescence and mitotic catastrophe in cancer therapy.

Authors:  Richa Singh; Jasmine George; Yogeshwer Shukla
Journal:  Cell Div       Date:  2010-01-21       Impact factor: 5.130

Review 2.  Aurora-A: a potential DNA repair modulator.

Authors:  Yan Wang; Huizhen Sun; Ziliang Wang; Mingming Liu; Zihao Qi; Jiao Meng; Jianmin Sun; Gong Yang
Journal:  Tumour Biol       Date:  2013-11-26
  2 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.