Downregulation of Telomerase in CoCl2-Induced Apoptosis of Myeloid Leukemic Cells
Ya-Bei Xua, Jing Zhangb, Evelyne Segal- Bendirdjianc, Ying-Li Wu a, *, Guo-Qiang Chen a, b, *
Identifiers and Pagination:Year: 2008
First Page: 74
Last Page: 80
Publisher Id: TOHJ-2-74
Article History:Received Date: 18/04/2008
Revision Received Date: 22/04/2008
Acceptance Date: 24/04/2008
Electronic publication date: 20/5/2008
Collection year: 2008
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Many reports showed that hypoxia-inducible factor-1α (HIF-1α), the main factor activated by hypoxia, plays a role in the transcriptional regulation of the human telomerase reverse transcriptase (hTERT), one of the critical elements of the oncogenic process. As a hypoxia-mimetic agent, cobalt chloride (CoCl2) can induce the accumulation of HIF-1α. Herein, we demonstrated that hTERT expression was greatly decreased during CoCl2-induced apoptosis in leukemic cell lines while overexpression of hTERT inhibited CoCl2-induced apoptosis. Knockdown of HIF-1α by shRNA in U937 cells did not abrogate CoCl2-induced hTERT downregulation nor CoCl2-induced apoptosis while inducible expression of HIF- 1α decreased the expression of hTERT. Furthermore, CoCl2 could decrease the c-myc protein in all the cells tested, no matter the HIF-1α was silenced or not. Taken together, we demonstrated that downregulation of hTERT contributes to CoCl2-induced apoptosis in leukemic cell lines and HIF-1α is not indispensable for CoCl2 induced downregulation of hTERT.