Accumulation and altered localization of telomere-associated protein TRF2 in immortally transformed and tumor-derived human breast cells
We have used cultured human mammary epithelial cells (HMEC) and breast tumor-derived lines to gain information on defects that occur during breast cancer progression. HMEC immortalized by a variety of agents (the chemical carcinogen benzo(a)pyrene, oncogenes c-myc and ZNF217, and/or dominant negative p53 genetic suppressor element GSE22) displayed marked up regulation (10-15 fold) of the telomere binding protein, TRF2. Up-regulation of TRF2 protein was apparently due to differences in post-transcriptional regulation, as mRNA levels remained comparable in finite life span and immortal HMEC. TRF2 protein was not up-regulated by the oncogenic agents alone in the absence of immortalization, nor by expression of exogenously introduced hTERT genes. We found TRF2 levels to be at least 2-fold higher than in control cells in 11/15 breast tumor cell lines, suggesting that elevated TRF2 levels are a frequent occurrence during the transformation of breast tumor cells in vivo. The dispersed distribution of TRF2 throughout the nuclei in some immortalized and tumor-derived cells indicated that not all the TRF2 was associated with telomeres in these cells. The process responsible for accumulation of TRF2 in immortalized HMEC and breast tumor-derived cell lines may promote tumorigenesis by contributing to the cells ability to maintain an indefinite life span.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE. Office of Management Budget and Evaluation; National Institutes of Health Grants CA-24844 and CA-108480, Department of Defense Grant DAMD17-01-1-0443; California Breast Cancer Research Program Grants 6JB-0133 and 8KB-0119
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 861307
- Report Number(s):
- LBNL-56752; R&D Project: 80YU01; TRN: US200601%%780
- Journal Information:
- Oncogene, Vol. 24, Issue 20; Related Information: Journal Publication Date: 05/05/05
- Country of Publication:
- United States
- Language:
- English
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