| Summary: | 碩士 === 國立陽明大學 === 生化暨分子生物研究所 === 98 === Rapamycin is a potential anti-cancer drug in clinical trial phase III. By inhibiting mTOR activity, rapamycin blocks 4E-BP1 phosphorylation and consequently decreases the activity of eIF4E in translation, leading to cancer cells susceptible to the growth inhibition. In this study, using various ESCC cell lines, we showed rapamycin can inhibit growth of tumor cells having a high protein ratio of 4E-BP1/eIF4E. Rapamycin resistance was found in TE2 cells that have a relative low 4E-BP1/eIF4E ratio, and restoration of rapamycin response was achieved in TE2 cells by increasing the protein ratio either through ectopic expression of 4E-BP1 or eIF4E knockdown. The defect of mdm2 translation inhibition by rapamycin was also observed in TE2 cells. Furthermore, we found the transcription of 4E-BP1 is under genetic and epigenetic regulation, which may account for the relative low expression of corresponding protein in this cell. Our results thus suggested that aberrant low 4E-BP1 expression, resulting in a low 4E-BP1/eIF4E ratio, can affect the efficacy of rapamycin in esophageal cancers.
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