Abstract
BackgroundBreast cancer is one the highest causes of female cancer death worldwide. Many standard chemotherapeutic agents currently used to treat breast cancer are relatively non-specific and act on all rapidly dividing cells. In recent years, more specific targeted therapies have been introduced. It is known that telomerase is active in over 90% of breast cancer tumors but inactive in adjacent normal tissues. The prevalence of active telomerase in breast cancer patients makes telomerase an attractive therapeutic target. Recent evidence suggests that telomerase activity can be suppressed by peroxisome proliferator activated receptor gamma (PPARγ). However, its effect on telomerase regulation in breast cancer has not been investigated.MethodsIn this study, we investigated the effect of the PPARγ ligand, troglitazone, on telomerase activity in the MDA-MB-231 breast cancer cell line. Real time RT-PCR and telomerase activity assays were used to evaluate the effect of troglitazone. MDA-MB-231 cells had PPARγ expression silenced using shRNA interference.ResultsWe demonstrated that troglitazone reduced the mRNA expression of hTERT and telomerase activity in the MDA-MB-231 breast cancer cell line. Troglitazone reduced telomerase activity even in the absence of PPARγ. In agreement with this result, we found no correlation between PPARγ and hTERT mRNA transcript levels in breast cancer patients. Statistical significance was determined using Pearson correlation and the paired Student's t test.ConclusionsTo our knowledge, this is the first time that the effect of troglitazone on telomerase activity in breast cancer cells has been investigated. Our data suggest that troglitazone may be used as an anti-telomerase agent; however, the mechanism underlying this inhibitory effect remains to be determined.
Highlights
Breast cancer is one the highest causes of female cancer death worldwide
In agreement with this result, we found that the expression of peroxisome proliferator activated receptor gamma (PPARg) protein was higher in MDA-MB-231 than the two other cell lines (Figure 1B)
Determining the mRNA expression level of human telomerase activity; telomerase reverse transcriptase (hTERT) and telomerase activity in MDA-MB-231 cells Results from real-time reverse transcription (RT)-PCR indicated that all three cell lines expressed hTERT mRNA (Figure 1C), and the telomeric repeat amplification protocol (TRAP) assay confirmed that telomerase was active in these cell lines (Figure 1D)
Summary
Breast cancer is one the highest causes of female cancer death worldwide. Many standard chemotherapeutic agents currently used to treat breast cancer are relatively non-specific and act on all rapidly dividing cells. It is known that telomerase is active in over 90% of breast cancer tumors but inactive in adjacent normal tissues. The terminal DNA at chromosome ends, known as telomeres, progressively shorten with each cell division and limit the replicative life span of human cells in culture [3]. Most human cancer cells maintain their telomeres through activation of telomerase (reviewed in [4]). In over 85% of human tumors, and more than 90% of breast carcinomas, telomerase is active whereas in normal tissues telomerase is active at low levels or is undetectable [5,6,7]. The inhibition of telomerase limits the growth of human cancer cells (reviewed in [4]), and various anti-telomerase strategies are currently under investigation in cancer patients
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