Downregulation of telomerase activity in HL60 cells by differentiating agents is accompanied by increased expression of telomerase-associated protein.

Telomerase activity provides a mechanism for the unlimited division potential of neoplastic cells. Induced differentiation of these cells was found to be associated with repression of telomerase activity irrespective of the inducing agent. We have employed a series of sublines of human promyelocytic leukemia line HL60 with differing degrees of resistance to differentiation to determine how tightly the expression of the differentiated phenotype is coupled to the downregulation of telomerase activity and to the expression of the recently identified telomerase-associated protein 1 (TP1). As expected, in the 1,25D3-dihydroxyvitamin D3 (1,25D3)-resistant subclones (20A-100A cells), telomerase activity was not significantly downregulated by 1,25D3 and, in most cases, by all-trans retinoic acid (atRA), to which these cells were cross-resistant, but telomerase activity was repressed by dimethylsulfoxide (DMSO) and phorbol-12-myristate-13-acetate (TPA), to which the sublines were in general sensitive. However, there were exceptions; in some instances telomerase activity was repressed in the absence of the expression of markers of differentiation. Also, there was an inverse relationship between telomerase activity and the cellular levels of TP1 transcripts. We conclude that in HL60 cells downregulation of telomerase is loosely associated with upregulation of differentiation markers and with other cellular changes which include an upregulation of TP1.