A novel glioblastoma cancer gene therapy using AAV-mediated long-term expression of human TERT C-terminal polypeptide
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AbstractGlioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism of rAAV-hTERTC27- mediated antitumor effects, we analyzed the global gene expression profiles of the rAAV-hTERTC27-treated tumor tissues and cell line as compared with that of the control rAAV-green fluorescent protein-treated samples by DNA microarray. Our results suggest that hTERTC27 exerts its effect through complex mechanisms, which involve genes regulating apoptosis, cell adhesion, cell cycle, immune responses, metabolism, signal transduction, transport, transcription and telomere maintenance.
All Author(s) ListNg SSM, Gao Y, Chau DHW, Li GHY, Lai LH, Huang PT, Huang CF, Huang JJ, Chen YC, Kung HF, Lin MCM
Journal nameCancer Gene Therapy
Year2007
Month6
Day1
Volume Number14
Issue Number6
PublisherNATURE PUBLISHING GROUP
Pages561 - 572
ISSN0929-1903
LanguagesEnglish-United Kingdom
KeywordsAAV; glioblastoma; hTERTC27
Web of Science Subject CategoriesBiotechnology & Applied Microbiology; BIOTECHNOLOGY & APPLIED MICROBIOLOGY; Genetics & Heredity; GENETICS & HEREDITY; Medicine, Research & Experimental; MEDICINE, RESEARCH & EXPERIMENTAL; Oncology; ONCOLOGY; Research & Experimental Medicine

Last updated on 2020-20-10 at 01:55