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標題: Transcriptionally mediated inhibition of telomerase of fungal immunomodulatory protein from Ganoderma tsugae in A549 human lung adenocarcinoma cell line
作者: Liao, C.H.
Hsiao, Y.M.
Hsu, C.P.
Lin, M.Y.
Wang, J.C.H.
Huang, Y.L.
Ko, J.L.
關鍵字: Ganoderma tsugae;fungal immunomodulatory protein;telomerase;breast-cancer cell;up-regulation;molecular-mechanisms;flammulina-velutipes;catalytic subunit;hepatoma-cells;htert gene;in-vivo;expression;apoptosis
Project: Molecular Carcinogenesis
期刊/報告no:: Molecular Carcinogenesis, Volume 45, Issue 4, Page(s) 220-229.
Telomerase expression is the hallmark of tumor cells, and activation of this ribonucleoprotein complex may be a rate-limiting or critical step in cellular immortalization and oncogenesis. Fungal immunomodulatory protein, FIP-gts, has been isolated from Ganoderma tsugae. In the present study, we expressed and purified the recombinant fungal immunomodulatory protein reFIP-gts in E. coli. We found that reFIP-gts significantly and selectively inhibits the growth of A549 cancer cells while not affecting the growth of normal MRC-5 fibroblasts. The reFIP-gts suppression of telomerase activity is concentration-dependent, due to the downregulation of the telomerase catalytic subunit (hTERT). It also happens at the mRNA level. These results were confirmed by transient transfections of A549 cells with pGL3-Basic plasmid constructs containing the functional hTERT promoter and its E-box-deleted sequences cloned upstream of a luciferase reporter gene. With electrophoretic mobility shift assays and Western blotting, we demonstrated that in response to reFIP-gts, binding of c-myc transcriptional factor to the E-box sequence on the hTERT promoter is inhibited. These results show that reFIP-gts suppresses telomerase activity and inhibits transcriptional regulation of hTERT via a c-myc-responsive element-dependent mechanism. Our findings provide new insight into both the anticancer function of reFIP-gts and the regulation of hTERT/telomerase expression, which may be valuable in the development of a promising chemopreventive agent. (c) 2006 Wiley-Liss, Inc.
ISSN: 0899-1987
DOI: 10.1002/mc.20161
Appears in Collections:食品暨應用生物科技學系

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