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KMID : 0603519990040030168
Journal of Korean Association of Cancer Prevention
1999 Volume.4 No. 3 p.168 ~ p.168
Inhibition of Telomerase Activity by Retinoic Acids in Human Breast Cancer Cells and Immortalized Cells in vitro
Choi Sang-Ho

Kang Hyun-Kyung
Kim Nam-Deuk
Abstract
The effects of retinoic acids (RAs), all-trans RA, 9-cis RA, 13-cis RA, and a synthetic RA, N-(4-hydroxypheny) retinamide (4-HPR), on telomerase activity were investigated in human MCF-7 breast cancer cells and MCF-10A immortalized cells in vitro. The activation of telomerase and stabilization of telomerase are thought to be required for cellular immortality and oncogenesis. The effects of RAs were both dose-and time-dependent, and correlated with altered expression telomerase component genes, human telomerase RNA (hTR), human telomerase-associated protein1 (hTEP1), and human telomerase reverse transcriptase (hTERT). Reverse transcription-polymerase chain reaction analysis of the recently identified gene, hTERT that encodes a catalytic subunit of human telomerase, revealed strong correlation between the expression of hTERT mRNA and telomerase activity. The expression of hTERT was shown to be down-regulated by RAs, in contrast those of hTR and hTEP1 mRNA were unaffected. While, 4-HPR was more effective than other RAs in growth inhibition, but less effective on the inhibition of telomerase activity. These results indicate that RAs can potently reduce telomerase activity in breast cancer cells and immortalized cells in vitro, and suggest further consideration of this mechanism for the chemoprevention of breast cancer.
KEYWORD
Telomerase, Breast cancer cell, Cancer cell differentiation
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