Open Accessp16 INK4a ‐mediated suppression of telomerase in normal and malignant human breast cells
Author(s) -
Bazarov Alexey V.,
Van Sluis Marjolein,
Hines William C.,
Bassett Ekaterina,
Beliveau Alain,
Campeau Eric,
Mukhopadhyay Rituparna,
Lee Won Jae,
Melodyev Sonya,
Zaslavsky Yuri,
Lee Leonard,
Rodier Francis,
Chicas Agustin,
Lowe Scott W.,
Benhattar Jean,
Ren Bing,
Campisi Judith,
Yaswen Paul
Publication year - 2010
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2010.00599.x
Subject(s) - biology , cdkn2a , telomerase reverse transcriptase , telomerase , cancer research , histone h3 , gene silencing , p14arf , retinoblastoma protein , cell cycle , cyclin dependent kinase , histone , gene , tumor suppressor gene , carcinogenesis , genetics
Summary The cyclin‐dependent kinase inhibitor p16 INK4a ( 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.