Cancer Res Treat.
2002 Jun;34(3):223-233.
Changes of Telomerase Activity and Proliferation by Inhibition of Reverse Transcriptase Activity in Human Cancer Cell
- Affiliations
-
- 1Cancer Metastasis Research Center, Korea.
- 2Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
- 3Brain Korea 21 Project for Medicine Science, Yonsei University College of Medicine, Seoul, Korea.
- 4Department of Hemato-oncology, Korea University College of Medicine, Seoul, Korea.
- 5Lilly Korea, Ltd., Seoul, Korea.
Abstract
-
PURPOSE: Activation of telomerase is proposed to be an essential step in cancer cell immortalization and cancer progression. 3'-azido-2',3'-dideoxythymidine (AZT), a reverse transcriptase inhibitor, was reported to be incorporated in telomeric sequences of immortalized cells in culture and to suppress the activity of telomerase and the cell proliferation. In this study, after induction of cancer cell senescence with long-term treatment of AZT, we investigated the dynamics of telomerase subunits (hTERT, hTR, TEP), transcription factors (c-Myc, Mad1), telomerase activity, and finally, telomere length in a human breast cancer cell line.
MATERIALS AND METGODS: Human breast cancer cell (MDA-MB-231) was treated with AZT. Senescence was measured by senescence-associated beta-gal staining and apoptosis was counted by dTd enzyme assay. Telomerase activity (by TRAP assay), expression of telomerase subunit genes (by RT-PCR and real-time PCR) and telomere length (by Southern blot analysis) were measured after the AZT treatment.
RESULTS
We found evidences of senescence, apoptosis and growth delay after AZT treatment. In addition, AZT- treated cancer cells showed inhibition of telomerase activity and shortening of telomere length in a dose- and duration-dependent way. Among the telomerase subunits, hTERT and c-Myc were the first factors to change after AZT treatment, subsequently, followed by the changes of hTR, Mad1 and TEP.
CONCLUSION
The suppression of hTERT and c-Myc by AZT treatment was the initial genetic phenomenon, subsequently followed by the changes of hTR, Mad1 and TEP.
Keyword
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Detection of Telomerase Activity in Psoriasis Lesional Skin and Correlaton with Ki-67 Expression and Suppression by Retinoic Acid
- Telomerase Activity and Expression of hTR and TERT in Human Soft Tissue Sarcomas
- Change of the Expression of Human Telomerase Reverse Transcriptase mRNA and Human Telomerase RNA after Cisplatin and 5-Fluorouracil Exposure in Head and Neck Squamous Cell Carcinoma Cell Lines
- Telomerase Activity in Primary Lung Cancers
- The Change of Telomerase Activity by Cisplatin and 5-FU in Head and Neck Cancer Cell Lines
