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Doxorubicin enhances the expression of transgene under control of the CMV promoter in anaplastic thyroid carcinoma cells.

Abstract

We investigated the effect of doxorubicin on transgene expression and evaluated the mechanism of enhanced transgene expression by doxorubicin in transfected human anaplastic thyroid cancer cells (ARO cells).

METHODS

ARO cells were transfected with plasmid vectors or adenoviral vectors expressing human sodium/iodide symporter (hNIS) or luciferase (Luc) under the control of cytomegalovirus (CMV) promoter. After treating transfected and control ARO cells with doxorubicin, iodide uptake assay and luciferase assay were performed. Reversed-phase polymerase chain reaction analysis for hNIS and Western blot analysis for IkappaB protein were executed. Electrophoretic mobility-shift assay (EMSA) was performed to evaluate nuclear factor-kappaB (NF-kappaB) binding activity induced by doxorubicin. Scintigraphic and bioluminescent images were acquired and quantitated before and after doxorubicin in a tumor-bearing mouse model.

RESULTS

Radioiodide uptake in ARO cells transfected with the NIS gene under the CMV promoter was remarkably enhanced by doxorubicin, and this corresponded to a significant increase in NIS messenger RNA. In addition, luciferase gene upregulation by doxorubicin was also observed in luciferase gene transfected ARO cells. These results were verified by in vivo imaging in a tumor-bearing mouse model. Moreover, transgene expressional enhancement by doxorubicin was observed after transfecting ARO cells with adenoviral vector or plasmid vector, when transgenes were under the control of a CMV promoter. In addition, NF-kappaB, activated by doxorubicin, induced transgene transcription under the control of the CMV promoter, which possesses an NF-kappaB binding site.

CONCLUSION

These findings indicate that doxorubicin enhances transgene expression under the control of the CMV promoter and that doxorubicin might be used as an adjuvant to radioiodine therapy by NIS gene transfer in anaplastic thyroid carcinoma.

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  • Authors+Show Affiliations

    ,

    Department of Nuclear Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Jongno-gu, Seoul 110-744, Korea.

    , , , , ,

    Source

    MeSH

    Animals
    Antibiotics, Antineoplastic
    Cell Line, Tumor
    Combined Modality Therapy
    Cytomegalovirus
    Doxorubicin
    Genetic Therapy
    Humans
    I-kappa B Proteins
    Iodine Radioisotopes
    Male
    Mice
    Mice, Nude
    Promoter Regions, Genetic
    Radiotherapy, Adjuvant
    Symporters
    Thyroid Neoplasms
    Transfection
    Transgenes

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17704247

    Citation

    Kim, Kwang Il, et al. "Doxorubicin Enhances the Expression of Transgene Under Control of the CMV Promoter in Anaplastic Thyroid Carcinoma Cells." Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, vol. 48, no. 9, 2007, pp. 1553-61.
    Kim KI, Kang JH, Chung JK, et al. Doxorubicin enhances the expression of transgene under control of the CMV promoter in anaplastic thyroid carcinoma cells. J Nucl Med. 2007;48(9):1553-61.
    Kim, K. I., Kang, J. H., Chung, J. K., Lee, Y. J., Jeong, J. M., Lee, D. S., & Lee, M. C. (2007). Doxorubicin enhances the expression of transgene under control of the CMV promoter in anaplastic thyroid carcinoma cells. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, 48(9), pp. 1553-61.
    Kim KI, et al. Doxorubicin Enhances the Expression of Transgene Under Control of the CMV Promoter in Anaplastic Thyroid Carcinoma Cells. J Nucl Med. 2007;48(9):1553-61. PubMed PMID: 17704247.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Doxorubicin enhances the expression of transgene under control of the CMV promoter in anaplastic thyroid carcinoma cells. AU - Kim,Kwang Il, AU - Kang,Joo Hyun, AU - Chung,June-Key, AU - Lee,Yong Jin, AU - Jeong,Jae Min, AU - Lee,Dong Soo, AU - Lee,Myung Chul, Y1 - 2007/08/17/ PY - 2007/8/21/pubmed PY - 2007/12/6/medline PY - 2007/8/21/entrez SP - 1553 EP - 61 JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine JO - J. Nucl. Med. VL - 48 IS - 9 N2 - UNLABELLED: We investigated the effect of doxorubicin on transgene expression and evaluated the mechanism of enhanced transgene expression by doxorubicin in transfected human anaplastic thyroid cancer cells (ARO cells). METHODS: ARO cells were transfected with plasmid vectors or adenoviral vectors expressing human sodium/iodide symporter (hNIS) or luciferase (Luc) under the control of cytomegalovirus (CMV) promoter. After treating transfected and control ARO cells with doxorubicin, iodide uptake assay and luciferase assay were performed. Reversed-phase polymerase chain reaction analysis for hNIS and Western blot analysis for IkappaB protein were executed. Electrophoretic mobility-shift assay (EMSA) was performed to evaluate nuclear factor-kappaB (NF-kappaB) binding activity induced by doxorubicin. Scintigraphic and bioluminescent images were acquired and quantitated before and after doxorubicin in a tumor-bearing mouse model. RESULTS: Radioiodide uptake in ARO cells transfected with the NIS gene under the CMV promoter was remarkably enhanced by doxorubicin, and this corresponded to a significant increase in NIS messenger RNA. In addition, luciferase gene upregulation by doxorubicin was also observed in luciferase gene transfected ARO cells. These results were verified by in vivo imaging in a tumor-bearing mouse model. Moreover, transgene expressional enhancement by doxorubicin was observed after transfecting ARO cells with adenoviral vector or plasmid vector, when transgenes were under the control of a CMV promoter. In addition, NF-kappaB, activated by doxorubicin, induced transgene transcription under the control of the CMV promoter, which possesses an NF-kappaB binding site. CONCLUSION: These findings indicate that doxorubicin enhances transgene expression under the control of the CMV promoter and that doxorubicin might be used as an adjuvant to radioiodine therapy by NIS gene transfer in anaplastic thyroid carcinoma. SN - 0161-5505 UR - https://www.unboundmedicine.com/medline/citation/17704247/Doxorubicin_enhances_the_expression_of_transgene_under_control_of_the_CMV_promoter_in_anaplastic_thyroid_carcinoma_cells_ L2 - http://jnm.snmjournals.org/cgi/pmidlookup?view=long&pmid=17704247 DB - PRIME DP - Unbound Medicine ER -