Do Telomerase Inhibitors Prevent the Spontaneous Immortalization of Breast Eptihelial Cells From Individuals Predisposed to Breast Cancer

摘要

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 shown that the inhibition of telomerase, by various types of inhibitors, led to the inhibition of cell growth via telomere-based mechanisms. To understand the mechanism of telomere shortening and growth inhibition, microarray analyses were performed to detect changes in the transcriptional profiling. The effects of telomerase inhibitors were found to be independent of p53 and pRB status. Furthermore, I showed that telomerase inhibitors and tamoxifen could prevent the spontaneous immortalization of Li-Fraumeni Syndrome- derived breast epithelial cells. Microarray analyses detected changes in the transcriptional profiling after treatment with tamoxifen and telomerase inhibitors. Also, Northern analyses of the spontaneously immortalized breast epithelial cells showed that while the cells were negative for estrogen receptor-alpha (ER alpha) by histology, the data show that the cells possibly contain ER beta. Tamoxifen mechanism's may be to utilize orphan receptors. These studies should lead to new insights in preventing the occurrence or recurrence of breast cancer.