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Alterations in p53 and E2F-1 function common to immortalized chicken embryo fibroblasts
1Department of Animal Science, University of Minnesota, St. Paul, Minnesota, MN 55108, USA.
Oncogene
|June 23, 2001
Summary
Newly developed immortal chicken embryo fibroblast (CEF) cells show unique genetic changes in p53 and E2F-1 regulation. These alterations, including cyclin gene upregulation, contribute to their continuous growth without telomerase activity.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Cellular immortalization is a key step in cancer development.
- Understanding the genetic basis of immortalization in non-viral, non-chemical models is crucial.
Purpose of the Study:
- To investigate the genetic alterations in immortalized chicken embryo fibroblast (CEF) cells.
- To determine the role of p53 and E2F-1 in CEF cell immortalization.
Main Methods:
- Reporter gene transcriptional activity assays
- DNA binding assays
- Northern blot analysis
- Analysis of mRNA and protein expression patterns
Main Results:
- Immortal CEF cells exhibited altered expression of p53 (down-regulated) and E2F-1 (up-regulated).
- Upregulation of most cyclin genes was observed, correlating with rapid cell division and serum-independent growth.
- Telomeric length and chromosome integrity were maintained without detectable telomerase activity.
Conclusions:
- Genetic alterations in p53 and E2F-1 regulation, unique to these CEF cells, contribute to immortalization.
- The findings provide insights into novel mechanisms of cellular immortalization beyond p53 and Rb pathway inactivation.