![](/images/graphics-bg.png)
Involvement of p53 Mutation and Mismatch Repair Proteins Dysregulation in NNK-Induced Malignant Transformation of Human Bronchial Epithelial Cells
Joint Authors
Zhang, Shuilian
Wang, Zhengyang
Huang, Xiaobin
Shen, Jing
Shen, Ying
Chen, Kailin
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-08-18
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Genome integrity is essential for normal cellular functions and cell survival.
Its instability can cause genetic aberrations and is considered as a hallmark of most cancers.
To investigate the carcinogenesis process induced by tobacco-specific carcinogen NNK, we studied the dynamic changes of two important protectors of genome integrity, p53 and MMR system, in malignant transformation of human bronchial epithelial cells after NNK exposure.
Our results showed that the expression of MLH1, one of the important MMR proteins, was decreased early and maintained the downregulation during the transformation in a histone modification involved and DNA methylation-independent manner.
Another MMR protein PMS2 also displayed a declined expression while being in a later stage of transformation.
Moreover, we conducted p53 mutation analysis and revealed a mutation at codon 273 which led to the replacement of arginine by histidine.
With the mutation, DNA damage-induced activation of p53 was significantly impaired.
We further reintroduced the wild-type p53 into the transformed cells, and the malignant proliferation can be abrogated by inducing cell cycle arrest and apoptosis.
These findings indicate that p53 and MMR system play an important role in the initiation and progression of NNK-induced transformation, and p53 could be a potential therapeutic target for tobacco-related cancers.
American Psychological Association (APA)
Shen, Ying& Zhang, Shuilian& Huang, Xiaobin& Chen, Kailin& Shen, Jing& Wang, Zhengyang. 2014. Involvement of p53 Mutation and Mismatch Repair Proteins Dysregulation in NNK-Induced Malignant Transformation of Human Bronchial Epithelial Cells. BioMed Research International،Vol. 2014, no. 2014, pp.1-12.
https://search.emarefa.net/detail/BIM-508196
Modern Language Association (MLA)
Shen, Ying…[et al.]. Involvement of p53 Mutation and Mismatch Repair Proteins Dysregulation in NNK-Induced Malignant Transformation of Human Bronchial Epithelial Cells. BioMed Research International No. 2014 (2014), pp.1-12.
https://search.emarefa.net/detail/BIM-508196
American Medical Association (AMA)
Shen, Ying& Zhang, Shuilian& Huang, Xiaobin& Chen, Kailin& Shen, Jing& Wang, Zhengyang. Involvement of p53 Mutation and Mismatch Repair Proteins Dysregulation in NNK-Induced Malignant Transformation of Human Bronchial Epithelial Cells. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-12.
https://search.emarefa.net/detail/BIM-508196
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-508196