Document Detail

p53-independent down-regulation of cyclin D1 and p21Waf1 in the process of immortalization of human esophageal epithelial cells.
MedLine Citation:
PMID:  9458357     Owner:  NLM     Status:  MEDLINE    
Immortalization is considered to be an initial critical step in the process of multistage cell transformation. However, the molecular mechanisms underlying this event are not well understood. Our laboratory previously established the immortalized human esophageal epithelial cell line, HET-1A, by SV40 T-antigen transfection. In the present study, we investigated the role of G1 cyclins and cyclin dependent kinase inhibitors, in the process of immortalization. By using immunoprecipitation and Western blot analysis, sequential changes in the expression of both cyclin D1 and p21Waf1 were detected during the conversion of precrisis esophageal epithelial cells to immortalized HET-1A cells. Reduced expression levels of both cyclin D1 and p21Waf1 were found in early passage and late passage immortalized cells when compared to levels in precrisis cells. In addition, continued subculture of the immortalized cells led to increased expression levels of both cyclin D1 and p21Waf1. No significant changes in the expression of either cyclin E or p53 were observed in early or late passage immortalized cells when compared to precrisis cells. These results suggest that changes in the expression levels of cyclin D1 and p21Waf1, but not cyclin E, may be important for immortalization and continued propagation of human esophageal epithelial cells, and these changes are not dependent on regulation by p53.
H Wang; E A Spillare; Q S Wang; Sabourin CLK; G D Stoner
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of oncology     Volume:  12     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  1998 Feb 
Date Detail:
Created Date:  2001-02-23     Completed Date:  2001-03-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  GREECE    
Other Details:
Languages:  eng     Pagination:  325-8     Citation Subset:  IM    
Division of Environmental Health Sciences, The Ohio State University School of Public Health, and The Ohio State University Comprehensive Cancer Center, CHRI Suite 1148, Columbus, OH 43210-1240, USA.
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MeSH Terms
Antigens, Polyomavirus Transforming
Blotting, Western
Cell Cycle
Cell Line
Cell Transformation, Neoplastic
Cyclin D1 / metabolism*
Cyclin E / metabolism
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / metabolism*
Enzyme Inhibitors / metabolism*
Epithelial Cells / metabolism
Esophagus / cytology*
Precipitin Tests
Tumor Suppressor Protein p53 / physiology*
Grant Support
Reg. No./Substance:
0/Antigens, Polyomavirus Transforming; 0/CDKN1A protein, human; 0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Enzyme Inhibitors; 0/Tumor Suppressor Protein p53; 136601-57-5/Cyclin D1

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