Document Detail


Abrupt reduction of c-myc expression by antisense RNA inducing terminal differentiation and apoptosis of a human esophageal cancer cell line.
MedLine Citation:
PMID:  7626199     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A human esophageal cancer cell line (EC8712) expressing high-level Myc protein was infected with recombinant retroviral particles (pA-BD9) at a multiplicity of infection (MOI) 1:1. This viral particle contains a neomycin-resistant gene and a 1.53-kb antisense RNA spanning the 2nd exon and its flanking sequences of the human c-myc oncogene. The G418-resistant EC8712 clones showed an 86% inhibition of growth rate and morphological changes characteristic of terminal differentiation and apoptosis. A decrease of about 80% of Myc protein was also observed in these infected cells by ABC-ELISA assay. 12-24 h after the infection of EC8712 cells with pA-BD9 at a high viral particle concentration (MOI = 1:10), the integration of the extrinsic 1.53-kb antisense c-myc fragment into the cancer cell genome was evidenced by the Southern blot analysis. Northern blot analyses showed the expression of this antisense fragment and a decrease of the intrinsic c-myc expression by 74% in comparison with that of the parental EC8712 cells. Heterotransplants of the infected EC8712 cells into the nude mice revealed a substantial decrease in tumorigenicity and morphological changes characteristic of terminal differentiation and apoptosis. Primary monolayer cell cultures of normal epithelia derived from the fetal and adult esophagus mucosa were set as controls. No noticeable increase in c-myc expression was found in these cultures. Infection of these cells with the same recombinant viral particles neither affected the growth rate of the cells nor their normal morphology. Our experiments indicate that the drastic decrease of the over-expressed Myc protein in cancer cells may also be an entrance to one of many pathways leading to the terminal differentiation and programmed cell death.
Authors:
X Zhao; X Wang; C Zhou; R Peng; S Yan; M Wu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Science in China. Series B, Chemistry, life sciences & earth sciences     Volume:  38     ISSN:  1001-652X     ISO Abbreviation:  Sci. China, Ser. B, Chem. Life Sci. Earth Sci.     Publication Date:  1995 May 
Date Detail:
Created Date:  1995-09-07     Completed Date:  1995-09-07     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8913082     Medline TA:  Sci China B     Country:  CHINA    
Other Details:
Languages:  eng     Pagination:  580-9     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Cell Transformation, Neoplastic
Esophageal Neoplasms / genetics*,  pathology,  virology
Genes, myc*
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Proto-Oncogene Proteins c-myc / biosynthesis*
RNA, Antisense*
Recombinant Proteins / genetics
Retroviridae / genetics
Transfection
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-myc; 0/RNA, Antisense; 0/Recombinant Proteins

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