Activity of the Human Telomerase Catalytic Subunit (hTERT) Gene Promoter Could Be Increased by the SV40 Enhancer

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概要

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• Telomerase is a ribonucleoprotein complex of which the function is to add telomeric repeats to chromosomal ends. Telomerase consists of two essential components, the telomerase RNA template (hTR) and the catalytic subunit (hTERT). hTERT is expressed only in cells and tissues positive for telomerase activity, i.e., tumor and fetal cells. The aim of this study is to test the increased telomerase promoter activity for cancer gene therapy in adenovirus vector. We cloned the hTERT promoter in place of the SV40 promoter in the pGL3-contol vector to be increased by the SV40 enhancer sequences, resulting in strong expression of luc+ only in telomerase positive cancer cells. Then we transfected the constructed plasmid into a normal human cell line and several cancer cell lines. Through these experiments, we identified the selective and increased expression of the luciferase gene controlled by the hTERT promoter and the SV40 enhancer in the telomerase positive cancer cell lines. To investigate the possibility of utilizing the hTERT promoter and the SV40 enhancer in targeted cancer gene therapy, we constructed an adenovirus vector expressing HSV-TK controlled by the hTERT promoter and the SV40 enhancer for the induction of specific telomerase positive cancer cell death. NSCLC cells infected by Ad-hT-TK-enh were more significantly suppressed and induced apoptosis than those infected by Ad-hT-TK. Telomerase is activated in 80∼90% of cancers, so adenovirus with increasing telomerase promoter activity might be used for targeted cancer gene therapy using suicide genes. These results show that the hTERT promoter and the SV40 enhancer might be used for targeted cancer gene therapy.

• 社団法人 日本農芸化学会の論文
• 2004-08-23

著者

• Song J‐s

  Korea Univ. Seoul Kor

• Song Joon-seok

  Institute Of Biotechnology Korea University

関連論文

• Adenovirus-Mediated Suicide SCLC Gene Therapy Using the Increased Activity of the hTERT Promoter by the MMRE and SV40 Enhancer
• Activity of the Human Telomerase Catalytic Subunit (hTERT) Gene Promoter Could Be Increased by the SV40 Enhancer
• Adenovirus-mediated Suicide Gene Therapy Using the Human Telomerase Catalytic Subunit (hTERT) Gene Promoter Induced Apoptosis of Ovarian Cancer Cell Line(Biochemistry & Molecular Biology)
• Enhanced Expression of Apoptin by the Myc-Max Binding Motif and SV40 Enhancer for SCLC Gene Therapy

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