Do Telomerase Inhibitors Prevent the Spontaneous Immortalization of Breast Epithelial Cells from Individuals Predisposed to Breast Cancer

摘要

13. Abstract (Maximum 200 Words) (abstract should contain no prnpnetary or confidential information) The activity of telomerase has been shown to be absent in normal somatic cells, with the exception of stem cells. The reactivation of telomerase has been seen as an early event in most cancers, especially breast cancer. I have previously shown that the inhibition of telomerase led to the inhibition of cell growth via telomere-based mechanisms. During the second year, to understand the mechanism of telomere shortening and growth inhibition, microarray analyses were performed to detect changes in the transcriptional profiling. Also during the second year, another type of telomerase inhibitor, oligonucleotide phosphoramidates, was shown to be an efficient telomerase inhibitor and potential therapeutic agent. Furthermore, I previously showed that telomerase inhibitors and tamoxifen could prevent the spontaneous immortalization of Li-Fraumeni Syndrome- derived breast epithelial cells. During the second year, microarray analyses detected changes in the transcriptional profiling after treatment. Also, preliminary Northern analyses of the spontaneously immortalized breast epithelial cells showed that while the cells were negative for estrogen receptor-alpha (ERoc) by histology, the data show that the cells possibly contain ER%. Tamoxifen mechanism may be to utilize orphan receptors. These studies should lead to new insi%hts in preventin% the occurrence or recurrence of breast cancer.