期刊
CANCER LETTERS
卷 310, 期 2, 页码 232-239出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2011.07.009
关键词
All-trans retinoic acid; Cellular senescence; p16; p21; p27
类别
资金
- National Research Foundation of Korea (NRF)
- Korea government (MEST) [2009-0070867]
- National Research Foundation of Korea [2009-0070867] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
We here present a new anti-tumor mechanism of all-trans retinoic acid (ATRA). ATRA induced several biomarkers of cellular senescence including irreversible G(1) arrest, morphological changes, senescence-associated beta-galactosidase, and heterochromatin foci in HepG2 cells. ATRA also upregulated levels of p16, p21, and p27 which lead to activation of Rb and subsequent inactivation of E2F1. These effects were abolished by the RNA interference-mediated silencing of p16, p21, and p27. Moreover, ATRA failed to induce cellular senescence in Huh7 and HCT116, in which p16, p21, and p27 were not upregulated by ATRA, confirming that ATRA induces cellular senescence via upregulation of p16, p21, and p27. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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