Suppression of telomerase reverse transcriptase (hTERT) expression in differentiated HL-60 cells: regulatory mechanisms

Telomerase activity, associated with cellular immortalization and tumorigen esis, is suppressed during terminal differentiation of HL-60 promyelocytic leukaemic cells. However, it is poorly understood how telomerase activity i s regulated in differentiated HL-60 cells. In the present study, we demonst rate that the down-regulation of telomerase reverse transcriptase (hTERT) e xpression, the catalytic subunit, occurs prior to the suppression of telome rase activity in differentiated HL-60 cells. In contrast, the expression of telomerase RNA template (hTR) and telomerase associated protein (TP1) is n ot reduced. This down-regulation of hTERT expression is achieved through in hibition of gene transcription, in which process new protein synthesis is r equired. Moreover, the rapid down-regulation of hTERT expression followed b y the inhibition of telomerase activity is a specific component of the diff erentiation programme and not simply a consequence of cell cycle arrest. Se rum-deprivation of HL-60 cells causes cell cycle arrest without differentia tion and this does not result in a significant reduction in hTERT mRNA leve ls within the first 24 h. Our findings suggest that hTERT expression is str ingently controlled at transcriptional level in HL-60 cells. The downregula tion of hTERT expression in the HL-60 cell differentiation model may repres ent a general regulatory mechanism through which telomerase becomes repress ed during development and differentiation of human somatic cells.