Document Detail


E1A inhibits the proliferation of human cervical cancer cells (HeLa cells) by apoptosis induction through activation of HER-2/Neu/Caspase-3 pathway.
MedLine Citation:
PMID:  18488161     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: This study is to investigate the inhibitory effect of E1A gene on the cell proliferation of HeLa cells and its mechanism related to apoptosis. METHODS: MTT assay and soft agar colony formation assay were employed to justify the inhibition activity of E1A on the proliferation of HeLa cells transfected with E1A gene. Western Blot, RT-PCR and Real-time quantitative RT-PCR were used to detect the gene expression of E1A, HER-2/Neu and Caspase-3 in HeLa cells, respectively. The Caspase-3 activity was monitored by ApoAlert Caspase-3 Assay. The redistribution of cell cycles and apoptosis of HeLa cells regulated by E1A expression were evaluated by flow cytometry. RESULTS: E1A expression significantly inhibits the cell proliferation and anchorage-independent cell growth of HeLa, with the respective highest inhibition rate of 40.7% and 43.4% (P < 0.01). HER-2/Neu expression in HeLa was significantly down-regulated by E1A, while the protein expression and activity of Caspase-3 was up-regulated by E1A expression. Flow cytometry revealed that E1A transfection in HeLa increased the cell number at G1 stage and simultaneously decreased the cell number at S stage. E1A transfection induced 8.71% of HeLa cells at apoptosis status. CONCLUSIONS: E1A significantly inhibits the cell proliferation of HeLa by the apoptosis induction through HER-2/Neu/Caspase-3 pathway. These results encourage us to continue an in-vivo study and preclinical development of LPD-E1A as a novel gene therapeutic agent for human cervical cancer.
Authors:
Liangfang Shen; Shan Zeng; Jia Chen; Meizuo Zhong; Huixiang Yang; Ruojing Yao; Hong Shen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-28
Journal Detail:
Title:  Medical oncology (Northwood, London, England)     Volume:  25     ISSN:  1357-0560     ISO Abbreviation:  Med. Oncol.     Publication Date:  2008  
Date Detail:
Created Date:  2008-05-19     Completed Date:  2008-07-29     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9435512     Medline TA:  Med Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  222-8     Citation Subset:  IM    
Affiliation:
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
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MeSH Terms
Descriptor/Qualifier:
Adenovirus E1A Proteins / analysis,  genetics*
Apoptosis*
Caspase 3 / physiology*
Cell Proliferation
Enzyme Activation
Female
Gene Therapy*
Hela Cells
Humans
RNA, Messenger / analysis
Receptor, erbB-2 / physiology*
Uterine Cervical Neoplasms / therapy*
Chemical
Reg. No./Substance:
0/Adenovirus E1A Proteins; 0/RNA, Messenger; EC 2.7.10.1/ERBB2 protein, human; EC 2.7.10.1/Receptor, erbB-2; EC 3.4.22.-/Caspase 3

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