Y. Yokoyama et al., Attenuation of telomerase activity by a hammerhead ribozyme targeting the template region of telomerase RNA in endometrial carcinoma cells, CANCER RES, 58(23), 1998, pp. 5406-5410
Telomerase activity is found in almost all carcinoma cells but not in most
somatic cells, suggesting that telomerase is an excellent target for cancer
therapy, We designed hammerhead ribozymes against human telomerase RNA and
studied their possible use as a tool for cancer therapy, Three ribozymes t
argeting the 3' end of the GUC sequence at 33-35 (the template region), 168
-170, and 313-315 from the 5' end of telomerase RNA were designed. In a cel
l-free system, these three hammerhead ribozymes efficiently cleaved the RNA
substrate. When these ribozyme RNAs were introduced into Ishikawa cells, w
hich are endometrial carcinoma cells, only a ribozyme targeting the RNA tem
plate region could diminish the telomerase activity, Next we subcloned the
ribozyme sequence into an expression vector and introduced this into AN3CA
cells, which are endometrial carcinoma cells. The clones that were obtained
showed reduced telomerase activity and telomerase RNA with expression of t
he ribozyme. These data suggest that the ribozyme against the RNA template
region is a good tool to repress telomerase activity in cancer cells.