Do Telomerase Inhibitors Prevent the Spontaneous Immortalization of Breast Epithelial Cell from Individuals Predisposed to Breast Cancer?
Annual rept. 1 Jul 2000-30 Jun 2001
TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
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Telomerase, a ribonucleoprotein reverse transcriptase, has been detected in reproductive cells, immortal cell lines, and most cancer cells. 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. In the first year I showed that the inhibition of telomerase led to the inhibition of cell growth via telomere-based mechanisms. The inhibition of telomerase was correlated with progressive telomere shortening in these cells and, consequently, inhibition of cell growth via cell death. Furthermore, I was able to show that telomerase inhibitors can prevent the spontaneous immortalization of Li-Fraumeni Syndrome-derived breast epithelial cells, which have not reached cellular crisis, by the prevention of telomerase activation. Tamoxifen also reduced the frequency of spontaneous immortalization in these cells. Since cancer is mostly a disease of epithelial cells, we believe our unique system of normal and spontaneously immortalized human breast epithelial cells should provide a good model system to examine the effects of tamoxifen and telomerase inhibitors. These studies should lead to new insights in preventing the occurrence or recurrence of breast cancer.
- Anatomy and Physiology
- Medicine and Medical Research