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Open Access Research article

Troglitazone suppresses telomerase activity independently of PPARγ in estrogen-receptor negative breast cancer cells

Fariborz Rashid-Kolvear12, Michael AS Taboski345, Johnny Nguyen1, Dong-Yu Wang2, Lea A Harrington346 and Susan J Done123*

Author Affiliations

1 Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

2 Division of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Ontario, M5G 2M9, Canada

3 Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

4 Campbell Family Institute for Breast Cancer Research, Toronto, Ontario, M5G 2C1, Canada

5 Department of Biochemistry and Molecular Biology, Dalhousie University, Tupper Medical Building, 5850 College St, 11-N2, Halifax, NS, B3H 1X5, Canada

6 Wellcome Trust Centre for Cell Biology, Michael Swann Building, rm. 5.18, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR. United Kingdom

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BMC Cancer 2010, 10:390  doi:10.1186/1471-2407-10-390

Published: 22 July 2010

Abstract

Background

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. 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.

Methods

In 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.

Results

We 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.

Conclusions

To 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.