Medical College of Wisconsin
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p53-independent down-regulation of cyclin D1 and p21Waf1 in the process of immortalization of human esophageal epithelial cells. Int J Oncol 1998 Feb;12(2):325-8

Date

02/12/1998

Pubmed ID

9458357

DOI

10.3892/ijo.12.2.325

Scopus ID

2-s2.0-0031885012 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

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.

Author List

Wang H, Spillare EA, Wang QS, Sabourin CLK, Stoner GD



MESH terms used to index this publication - Major topics in bold

Antigens, Polyomavirus Transforming
Blotting, Western
Cell Cycle
Cell Line
Cell Transformation, Neoplastic
Cyclin D1
Cyclin E
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
Down-Regulation
Enzyme Inhibitors
Epithelial Cells
Esophagus
Humans
In Vitro Techniques
Precipitin Tests
Tumor Suppressor Protein p53