利用合成改良之癌症專一性啟動子進行肺癌之基因治療
Date Issued
2005-07-31
Date
2005-07-31
Author(s)
陳晉興
DOI
932314B002237
Abstract
Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer death
in Taiwan and numerous developed countries. No obvious improvement in survival
can be achieved in recent years although various efforts have been made. As the
pathogenesis and biology of tumors are becoming clear, gene therapy could be an
attractive modality for the treatment of lung cancer. Most gene therapy approaches
currently use nonspecific, nonselective prokaryotic promoters such as the CMV
promoter that can be expressed at high levels in normal cells, potentially contributing
to toxicity. An alternative approach would be to use a tissue- or tumor-specific
promoter to limit the spectrum of cells that express the gene therapy construct. In the
previous studies, we have shown in vitro and in vivo that the activation of the survivin
promoter is lung cancer specific. In this study, we choose another promoter, the
GRP-78 (glucose-regulated protein 78) promoter to evaluate its future application in
lung cancer gene therapy. Our preliminary data showed that the GRP-78 promoter
was cancer-specific in cell line studies. To enhance its activity, the CMV and GRP
enhancers were added at the upstream of the GRP-78 promoter. It appeared that both
the CMV enhancer and GRP enhancer could increase the activity of the GRP
promoter, respectively, while the cancer-specificity remained unchanged. By using
this modified GRP-78 promoter, we showed that the activity and cancer specificity of
this promoter is better than the CMV promoter in both cell lines and xenograft animal
studies. The promising results of this study indicate the potential use of the modified
GRP-78 promoter in cancer gene therapy.
Subjects
lung cancer
gene therapy
survivin
GRP
BIK
SDGs
Publisher
臺北市：國立臺灣大學醫學院外科
Type
report
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