Document Detail


Antisense targeting human papillomavirus type 16 E6 and E7 genes contributes to apoptosis and senescence in SiHa cervical carcinoma cells.
MedLine Citation:
PMID:  17586029     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Human papillomavirus type 16 (HPV-16) is a high-risk DNA tumor virus involved in the development of cervical carcinomas. Substantial studies have demonstrated that E6 and E7 oncoproteins of HPV-16 could induce cell proliferation and immortalization. Repression of E6 and/or E7 oncogenes may induce cervical cancer cells to undergo apoptosis or senescence. The purpose of this study was to determine whether activation of the p53 and retinoblastoma (Rb) pathway by HPV-16 E6 and E7 repression was responsible for apoptosis and senescence of cervical cancer cells and to explore the potential of an antisense RNA (AS) transcript for gene therapy of cervical cancer. METHOD: The antisense RNA directed against HPV-16 E6 and E7 (16AS) was constructed, and its effects on cell apoptosis and senescence of SiHa cervical carcinoma cells harboring HPV-16 were analyzed. The efficiency of 16AS was evaluated with RT-PCR, Western blotting, flow cytometry analysis, Hoechst 33258 staining, senescent cell morphology observation and senescence-associated beta-galactosidase staining. RESULTS: The sufficient repression of HPV-16 E6 and E7 oncogenes were achieved in 16AS-transfected SiHa cells, which led to obvious apoptosis and replicative senescence of tumor cells. Furthermore, the downregulation of HPV-16 E6 and E7 by 16AS transfection resulted in remarkable increase of both p53 expression and hypophosphorylated p105Rb level in SiHa cells. CONCLUSION: These results demonstrate that reduction of E6 and E7 expression is sufficient to induce SiHa cells to undergo apoptosis and senescence and suggest that transfection of cervical cancer cells with HPV-16 E6 and E7 antisense RNA is a potential approach to treat HPV-16-positive cervical cancers.
Authors:
Ni Sima; Shixuan Wang; Wei Wang; Debo Kong; Qian Xu; Xu Tian; Aiyue Luo; Jianfeng Zhou; Gang Xu; Li Meng; Yunping Lu; Ding Ma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-21
Journal Detail:
Title:  Gynecologic oncology     Volume:  106     ISSN:  0090-8258     ISO Abbreviation:  Gynecol. Oncol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-30     Completed Date:  2007-09-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0365304     Medline TA:  Gynecol Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  299-304     Citation Subset:  IM    
Affiliation:
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan, Hubei 430030, PR China.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / genetics*
Cell Aging / genetics
Cell Line, Tumor
Female
Gene Therapy / methods
Green Fluorescent Proteins / genetics
Human papillomavirus 16 / genetics
Humans
Oncogene Proteins, Viral / genetics*
Papillomavirus Infections / genetics,  pathology,  virology
RNA, Antisense / genetics*
RNA, Messenger / biosynthesis,  genetics
Repressor Proteins / genetics*
Transfection
Uterine Cervical Neoplasms / genetics*,  pathology,  therapy,  virology
Chemical
Reg. No./Substance:
0/E6 protein, Human papillomavirus type 16; 0/Oncogene Proteins, Viral; 0/RNA, Antisense; 0/RNA, Messenger; 0/Repressor Proteins; 0/enhanced green fluorescent protein; 0/oncogene protein E7, Human papillomavirus type 16; 147336-22-9/Green Fluorescent Proteins

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