Suppression of Telomerase Reverse Transcriptase (hTERT) Expression in Differentiated HL-60 Cells: Regulatory Mechanisms

Br J Cancer. 1999 Jun;80(8):1156-61. doi: 10.1038/sj.bjc.6690480.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Differentiation
  • Cell Transformation, Neoplastic*
  • DNA-Binding Proteins
  • Gene Expression Regulation, Neoplastic*
  • HL-60 Cells
  • Humans
  • RNA*
  • Telomerase / biosynthesis*
  • Telomerase / metabolism*
  • Transcription, Genetic

Substances

  • DNA-Binding Proteins
  • telomerase RNA
  • RNA
  • Telomerase