Design of a Ribozyme to Inactivate Telomerase Activity in Breast Cancer Tumors

摘要

Telomerase expression has been associated with the immortality and metastasis of malignant breast cancer cells. Telomerase activity has been detected in several human cancers including breast carcinomas. However, telomerase activity is either very low or not detectable in normal cells of the body. These observations suggest the development of anti-telomerase strategies may prevent cancer cell division without adverse effects on normal cell populations. This investigation describes the development of a novel therapeutic approach directed against the telomerase complex required for cancer cell division. Catalytic RNA sequences, called ribozymes, will be expressed in breast cancer cell lines, to specifically recognize, cleave and eliminate the telomerase complex. This ribozyme therapy is designed to prevent tumor cell division and eliminate the metastatic potential of breast cancers. Retroviral vectors will deliver therapeutic genes encoding for the anti-telomerase ribozyme to breast cancer cells. Breast cancer cells expressing anti-telomerase ribozymes were observed to have reduced levels of hTERT mRNA, a reduction in telomerase activity and limited inhibition of cell proliferation. Further development is required to determine if ribozyme based gene therapy can be used as a strategy for the treatment of aggressive breast tumors.