Expression of the telomerase catalytic subunit, hTERT, induces resistance to transforming growth factor beta growth inhibition in p16INK4A(-) human mammary epithelial cells
Autor: | Martha R. Stampfer, Alain Philippe Vasserot, Serge Lichtsteiner, Gerri Levine, J C Garbe, Paul Yaswen |
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Rok vydání: | 2001 |
Předmět: |
Telomerase
Protein subunit Blotting Western Biology medicine.disease_cause chemistry.chemical_compound Transforming Growth Factor beta Catalytic Domain medicine Humans Telomerase reverse transcriptase Breast Cyclin-Dependent Kinase Inhibitor p16 Cell Line Transformed Multidisciplinary Epithelial Cells Transforming growth factor beta Telomere Biological Sciences Immunohistochemistry DNA-Binding Proteins chemistry Cancer research biology.protein RNA Ectopic expression Growth inhibition Carcinogenesis Cell Division |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 98(8) |
ISSN: | 0027-8424 |
Popis: | Failures to arrest growth in response to senescence or transforming growth factor β (TGF-β) are key derangements associated with carcinoma progression. We report that activation of telomerase activity may overcome both inhibitory pathways. Ectopic expression of the human telomerase catalytic subunit, hTERT, in cultured human mammary epithelial cells (HMEC) lacking both telomerase activity and p16 INK4A resulted in gaining the ability to maintain indefinite growth in the absence and presence of TGF-β. The ability to maintain growth in TGF-β was independent of telomere length and required catalytically active telomerase capable of telomere maintenance in vivo . The capacity of ectopic hTERT to induce TGF-β resistance may explain our previously described gain of TGF-β resistance after reactivation of endogenous telomerase activity in rare carcinogen-treated HMEC. In those HMEC that overcame senescence, both telomerase activity and TGF-β resistance were acquired gradually during a process we have termed conversion. This effect of hTERT may model a key change occurring during in vivo human breast carcinogenesis. |
Databáze: | OpenAIRE |
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