Gene therapy against gynecologic cancers targeting telomerase

点击翻译按钮获取中文摘要

Human telomerase is composed of three main subunit components, human telomerase RNA (hTR), telomerase-associated protein (TP1) and telomerase reverse transcriptase (hTERT). RT-PCR analyses demonstrated that expression of hTERT was observed in cancer tissues and cell lines, while hTR or TP1 was broadly expressed not only in cancers but also in normal tissues. Thus, hTERT expression was well correlated with telomerase activity.We succeeded to clone promoter sequences of hTERT gene. Of particular importance is identification of transcription factors interacting with such regions and regulate hTERT express in utilizing it for gene therapy. C-Myc has been shown to be a direct transactivator of hTERT gene. Antisense strategy against c-Myc has been in success to inhibit telomerase activity in cancer cells and suppress the tumor growth. As another strategy, we have applied hTERT promoter to plasmid or virus vectors for gene therapy. We have constructed a chimeric vector in which hTERT promoter is cloned upstream of apoptosis-inducing genes inhibiting cell growth and introduced of these vectors into cervical cancer cells. We have confirmed the specific inhibition of tumor growth in cell lines and animal models by these gene therapies.