Suppression of telomerase reverse transcriptase (hTERT) expression in differentiated HL-60 cells: regulatory mechanisms.
Telomerase activity, associated with cellular immortalization and tumorigenesis, is suppressed during terminal differentiation of HL-60 promyelocytic leukaemic cells. However, it is poorly understood how telomerase activity is regulated in differentiated HL-60 cells. In the present study, we demonstrate that the down-regulation of telomerase reverse transcriptase (hTERT) expression, the catalytic subunit, occurs prior to the suppression of telomerase activity in differentiated HL-60 cells. In contrast, the expression of telomerase RNA template (hTR) and telomerase associated protein (TP1) is not reduced. This down-regulation of hTERT expression is achieved through inhibition of gene transcription, in which process new protein synthesis is required. Moreover, the rapid down-regulation of hTERT expression followed by the inhibition of telomerase activity is a specific component of the differentiation programme and not simply a consequence of cell cycle arrest. Serum-deprivation of HL-60 cells causes cell cycle arrest without differentiation and this does not result in a significant reduction in hTERT mRNA levels within the first 24 h. Our findings suggest that hTERT expression is stringently controlled at transcriptional level in HL-60 cells. The downregulation of hTERT expression in the HL-60 cell differentiation model may represent a general regulatory mechanism through which telomerase becomes repressed during development and differentiation of human somatic cells.
Xu
D
D
Department of Medicine, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Gruber
A
A
Björkholm
M
M
Peterson
C
C
Pisa
P
P
D002453:Cell Cycle; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D012313:RNA; D019098:Telomerase / Q000096:biosynthesis* / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase