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- Title
Suppression of teratocarcinoma growth by soluble TRAIL gene from progression-elevated gene-3 promoter.
- Authors
Jiang, X. L.; Xia, H. Q.; Du, L. L.; Yang, S.; LU, G. X.
- Abstract
Introduction: Pluripotent embryonal carcinoma (EC) cells have the ability to self-renew in vitro and maintain their ability to differentiate into all three lineages: ectoderm, mesoderm and endoderm. At the same time, EC cells express a set of important pluripotent markers that are exclusive to human ES cells but are not expressed in the cells' differentiated derivatives. Hence, EC cells are stem cells of such tumours and are generally considered to be the malignant counterparts of human embryonic stem cells. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a potent inducer of apoptosis in various cancer cells, whereas normal cells are not sensitive to TRAIL-mediated apoptosis. The progressionelevated gene-3 (PEG-3) promoter displays elevated robust expression in a broad spectrum of human cancer cell lines with marginal expression in normal cellular counterparts. Materials/Methods: A vector expressing TRAIL amino acids 114-281 driven by progression-elevated gene-3 promoter (PEG-prom) was constructed. Transfection of the NTERA- 2 cell line and teratocarcinoma in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice with soluble TRAIL gene controlled by PEG-3 promoter and the results of EC cell apoptosis and the expression of mRNA level of DcR1, DcR2, DR4 and DR5 were evaluated by FACS and real-time PCR respectively. Results: Soluble TRAIL was able to induce obvious apoptosis of NTERA-2 cells and apoptotic cell accounted for 24.4 ± 2.1% of the population, elevate expression of DR4/DR5, suppress the tumour growth and prolong survival of the tumour-bearing mice. Histological examination of the tumours and serum analyses showed the absence of detectable TRAIL-induced toxicity in normal tissues including the liver. Conclusion: The successful inhibition of teratocarcinoma growth and the absence of detectable toxicty suggest a putative role for soluble TRAIL gene from PEG-3 promoter in the teratocarcinoma.
- Subjects
TUMORS; PLURIPOTENT stem cells
- Publication
Reproductive BioMedicine Online (Reproductive Healthcare Limited), 2008, Vol 16, Issue S2, pS-32
- ISSN
1472-6483
- Publication type
Abstract
- DOI
10.1016/S1472-6483(10)61551-9