인체 유방암 세포주에서 retinoic Acids의 Telomerase 활성 저해효과 연구
Inhibition of Telomerase Activity by Retinoic Acids in Human Breast Cancer Cells and Immortalized Cells in vitro
최상호, 강현경, 김남득,
소속 상세정보
최상호 ( Choi Sang-Ho )
부산대학교 약학대학
강현경 ( Kang Hyun-Kyung )
부산대학교 약학대학
김남득 ( Kim Nam-Deuk )
부산대학교 약학대학
KMID : 0603519990040030168
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.
키워드
Telomerase; Breast cancer cell; Cancer cell differentiation
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