Bazarov, A. V., van Sluis, M., Hines, W. C., Bassett, E., Beliveau, A., Campeau, E., Mukhopadhyay, R., Lee, W. J., Melodyev, S., Zaslavsky, Y., Lee, L., Rodier, F., Chicas, A., Lowe, S. W., Benhattar, J., Ren, B., Campisi, J., Yaswen, P. (October 2010) p16(INK4a)-mediated suppression of telomerase in normal and malignant human breast cells. Aging Cell, 9 (5). pp. 736-746. ISSN 1474-9718
Abstract
P>The cyclin-dependent kinase inhibitor p16INK4a (CDKN2A) is an important tumor suppressor gene frequently inactivated in human tumors. p16 suppresses the development of cancer by triggering an irreversible arrest of cell proliferation termed cellular senescence. Here, we describe another anti-oncogenic function of p16 in addition to its ability to halt cell cycle progression. We show that transient expression of p16 stably represses the hTERT gene, encoding the catalytic subunit of telomerase, in both normal and malignant breast epithelial cells. Short-term p16 expression increases the amount of histone H3 trimethylated on lysine 27 (H3K27) bound to the hTERT promoter, resulting in transcriptional silencing, likely mediated by polycomb complexes. Our results indicate that transient p16 exposure may prevent malignant progression in dividing cells by irreversible repression of genes, such as hTERT, whose activity is necessary for extensive self-renewal.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | heterochromatin histone methylation hTERT INK4a senescence EMBRYONIC STEM-CELLS REVERSE-TRANSCRIPTASE EXPRESSION RETINOBLASTOMA TUMOR-SUPPRESSOR MAMMARY EPITHELIAL-CELLS HISTONE H3 LYSINE-27 CELLULAR SENESCENCE HTERT GENE HETEROCHROMATIN FORMATION DEVELOPMENTAL REGULATORS DIFFERENTIAL ROLES |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders > cancer > cancer types > breast cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations therapies > stem cells |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Shared Resources > DNA Sequencing Service CSHL labs > Lowe lab CSHL Cancer Center Program > Cancer Genetics |
| Depositing User: | CSHL Librarian |
| Date: | October 2010 |
| Date Deposited: | 26 Sep 2011 13:46 |
| Last Modified: | 13 Oct 2015 19:28 |
| PMCID: | PMC2941554 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/15351 |
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