Correlating telomerase activity levels with human neuroblastoma outcomes

Abstract

Telomerase activity was analysed in 100 neuroblastoma cases. Although telomerase activity was not detected in normal adrenal tissues or benign ganglioneuromas, almost all neuroblastomas (94%) did express it, suggesting an important role for telomerase in neuroblastoma development. Neuroblastomas with high telomerase activity had other genetic changes (for example, N-myc amplification) and an unfavourable prognosis, whereas tumours with low telomerase activity were devoid of such genetic alterations and were associated with a favourable prognosis. Three neuroblastomas lacking telomerase activity regressed (stage IVS). Thus telomerase expression may be required as a critical step in the multigenetic process of tumorigenesis, and two different pathways may exist for the development of neuroblastoma.

Mortalization of human promyelocytic leukemia HL-60 cells to be more susceptible to sodium butyrate-induced apoptosis and inhibition of telomerase activity by down-regulation of nucleophosmin/B23

“…Activation or up-regulation of telomerase is a known feature of immortal cancer cells (Kim et al, 1994;Counter et al, 1992;Hiyama et al, 1995), and there is a reverse relationship between the degree of di erentiation and the level of telomerase activity down-regulation (Albanell et al, 1996;Bestilny et al, 1996). Down-regulation of telomerase activity (Bestilny et al, 1996) and nucleophosmin/B23 mRNA (Hsu and Yung, 1998) are observed in response to differentiation-inducing agent retinoic acid in HL-60 cells.…”

Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications

“…Following the development by Kim et al (1994) of an extremely sensitive PCR-based assay, telomerase activity has been found in a large variety of solid tumours, including neuroblastomas (Hiyama et al, 1995a), lung carcinomas (Hiyama et al, 1995b), hepatomas (Tahara et al, 1995a), gastric and colon carcinomas (Chadeneau et al, 1995;Hiyama et al, 1995c;Tahara et al, 1995bLi et al, 1996, breast carcinomas (Hiyama et al, 1996;Sugino et al, 1996) and brain tumours (Langford et al, 1995). In the present study, the activity of this enzyme was demonstrated in more than 90% of colorectal carcinomas in line with previous studies (Chadeneau et al, 1995;Tahara et al, 1995b;Li et al, 1996).…”

Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation

“…Conversely, introduction of pRB into tumor cell lines has been shown to repress telomerase activity (Xu et al, 1997). In addition, exposure of three di erent human leukemic cell lines to antisense c-myc oligonucleotides results in down-regulation of telomerase activity (Fujimoto and Takahashi, 1997); whereas Nmyc gene ampli®cation in neuroblastoma is associated with high telomerase activity (Hiyama et al, 1995). These observations, together with highly similar expression pro®les for mTERT and c-myc during mouse erythroleukemia (MEL) cell di erentiation and mitogen-stimulated lymphocyte proliferation (Greenberg et al, 1998;Lachman and Skoultchi, 1984;Reed et al, 1986), imply a potential link between increased Myc transactivation activity and up-regulation of TERT gene expression in normal proliferating and transformed cells.…”