Effects of telomerase switch in neuroblastoma cell lines

Activation of telomerase represents a key step in the malignant transformation process. Specific suppression of telomerase activity (TA) and of unlimited cell proliferation in tumour cells provide a rational basis for anticancer strategies.

We study the effects of expression of a dominant negative (DN) mutant of the telomerase catalytic unit (hTERT) and Wild type (WT) hTERT in the Neuroblastoma (NB) cell lines SKNSH (TA pos.) and CHLA90 (TA neg).

In CHLA90 cells expression of WT – hTERT induced TA and enhanced growth. In SKNSH cells WT – hTERT expression increased the overall TA and telomere length. Expression of hTERT (DN or WT) caused no measurable effects on telomere length in TA neg. cells.

Telomerase inactivation resulted in drastic telomere shortening and reduced proliferation activity in SKNSH cells.

These results indicate that specific, potent inhibition of hTERT is a very promising approach in limiting the growth of NB cells.

Further characterization of the modified cells regarding chemo/- radiosensitivity and expression profiling is under investigation.