Identification and characterization of rapidly dividing U937 clones with differential telomerase activity and gene expression profiles: role of c-Myc/Mad1 and Id/Ets proteins

Ets2 Maintains hTERT Gene Expression and Breast Cancer Cell Proliferation by Interacting with c-Myc

“…The specific effect of Ets2 retraction on the gene repression of hTERT in breast cancer cells reflects an important mechanism for the maintenance or up-regulation of hTERT gene transcription by Ets2. Thus, our findings do not support the paradox of Ets2 negative regulation of the hTERT gene by Ets2 overexpression (18,19), although we cannot exclude the possibility that Ets2 operates at the hTERT gene by partnering with another protein when Ets2 is overexpressed in a cell typespecific manner.…”

“…Individual clones were isolated and screened by PCR. Other Ets2 knockdown cell clones (clones [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] were also transfected in mass cell cultures. The transfection of hTERT was confirmed by telomerase activity assay and c-Myc expression was confirmed by Western blotting.…”

“…Xiao et al (18,19) showed that both Ets1 and Ets2 bind to the hTERT gene promoter and overexpression of either Ets1 or Ets2 inhibits telomerase activity, an effect independent of gene expression of c-Myc and Sp1 in human myeloid erythroleukemia K562 cells.…”

“…16). However, controversy remains as to whether Ets2 is a transcription factor (17) or repressor (18,19). Maida et al showed that mutation of a putative Ets binding site proximal to the transcription site (…”

Telomerase: The Devil Inside

“…Based on the current knowledge, it seems tempting to speculate that the same cis -regulatory elements can act as a site of positive and negative regulation of hTERT gene expression depending on the proliferation status, at least in some tissues; e.g., E-box binding by c-Myc activates the hTERT promoter whereas the binding of its counterpart Mad1 to the E-box sequences results in hTERT /telomerase downregulation [15,31,32]. Similarly, CEBP-α represses hTERT in normal breast cells, but CEBP-β activates it in breast cancer cells by binding to the same regulatory sites [33]; in resting hepatocytes, Rb factors repress hTERT expression whereas E2F2/E2F7 factors are involved in hTERT promoter activation in proliferating hepatocytes by binding to the same sequence [12].…”