Searching for Promoters to Drive Stable and Long-Term Transgene Expression in Fibroblasts for Syngeneic Mouse Tumor Models
| Autor: | Anastasiia K. Siniushina, I. V. Alekseenko, A. I. Kuzmich, Dina V. Antonova, V. V. Pleshkan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
BALB 3T3 Cells Genetic enhancement Cell Cytomegalovirus Gene Expression lcsh:Chemistry Mice Transduction (genetics) 0302 clinical medicine Neoplasms Transgenes Cloning Molecular Promoter Regions Genetic lcsh:QH301-705.5 Cells Cultured Spectroscopy Mice Inbred BALB C General Medicine Computer Science Applications Cell biology Cell Transformation Neoplastic medicine.anatomical_structure 030220 oncology & carcinogenesis Transgene mouse model Genetic Vectors Mice Transgenic Biology Article Catalysis Inorganic Chemistry 03 medical and health sciences fibroblasts medicine Animals Humans tumor microenvironment Physical and Theoretical Chemistry Molecular Biology Gene Tumor microenvironment promoter Organic Chemistry Promoter Disease Models Animal Transplantation Isogeneic HEK293 Cells 030104 developmental biology cell proliferation lcsh:Biology (General) lcsh:QD1-999 Cancer cell NIH 3T3 Cells |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 17 International Journal of Molecular Sciences, Vol 21, Iss 6098, p 6098 (2020) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21176098 |
| Popis: | Tumor is a complex system of interactions between cancer cells and other cells of the tumor microenvironment. The cancer-associated fibroblasts (CAFs) of the tumor microenvironment remain in close contact with the cancer cells and play an important role in cancer progression. Genetically, CAFs are more stable than cancer cells, making them an attractive target for genetic modification in gene therapy. However, the efficiency of various promoters for transgene expression in fibroblasts is scarcely studied. We performed a comparative analysis of transgene long-term expression under the control of strong cytomegalovirus promoter (pCMV), constitutive cell promoter of the PCNA gene (pPCNA), and the potentially fibroblast-specific promoter of the IGFBP2 gene (pIGFBP2). In vitro expression of the transgene under the control of pCMV in fibroblasts was decreased soon after transduction, whereas the expression was more stable under the control of pIGFBP2 and pPCNA. The efficiency of transgene expression was higher under pPCNA than that under pIGFBP2. Additionally, in a mouse model, pPCNA provided more stable and increased transgene expression in fibroblasts as compared to that under pCMV. We conclude that PCNA promoter is the most efficient for long-term expression of transgenes in fibroblasts both in vitro and in vivo. |
| Databáze: | OpenAIRE |
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