Retinoic acid receptors initiate induction of the cytomegalovirus enhancer in embryonal cells.

Ghazal, Peter; DeMattei, Cordell; Giulietti, Emi; Kliewer, Steven A.; Umesono, Kazuhiko; Evans, Ronald M.

doi:10.1073/pnas.89.16.7630

Cited by 59 publications

(47 citation statements)

References 43 publications

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“…In addition, we demonstrate that this enhancement is mediated by the activation of NF-kB. Moreover, because the CMV promoter has cis-regulatory elements recognized by various transcription factors-such as AP-1 (34), CREB (35), retinoic acid nuclear receptors (RARs) (36), and NF-kB (37)-further studies of other factors and combination treatments are required to help elucidate the reasons for improved transgene activity. Further experiments evaluating a prolonged accumulation of radionuclide and the tumorcidal effect of this improved method are also needed.…”

Section: Discussionmentioning

confidence: 99%

Doxorubicin Enhances the Expression of Transgene Under Control of the CMV Promoter in Anaplastic Thyroid Carcinoma Cells

Kim

Kang

Chung

et al. 2007

Journal of Nuclear Medicine

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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. Reversedphase polymerase chain reaction analysis for hNIS and Western blot analysis for IkB protein were executed. Electrophoretic mobility-shift assay (EMSA) was performed to evaluate nuclear factor-kB (NF-kB) 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 tumorbearing 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-kB, activated by doxorubicin, induced transgene transcription under the control of the CMV promoter, which possesses an NF-kB 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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Section: Discussionmentioning

confidence: 99%

Doxorubicin Enhances the Expression of Transgene Under Control of the CMV Promoter in Anaplastic Thyroid Carcinoma Cells

Kim

Kang

Chung

et al. 2007

Journal of Nuclear Medicine

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“…One of the promoters containing Gfi-1 binding sites is the HCMV MIE promoter, which regulates the expression of genes required for the initiation of HCMV infection and probably the reactivation of HCMV from latency (14,24). This promoter contains two sites with 79 and 80% homology to the Gfi-1 binding site consensus.…”

Section: Discussionmentioning

confidence: 99%

Gfi-1 Encodes a Nuclear Zinc Finger Protein That Binds DNA and Functions as a Transcriptional Repressor

Zweidler‐McKay

Grimes

Flubacher

et al. 1996

Molecular and Cellular Biology

277

285

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The Gfi-1 proto-oncogene encodes a zinc finger protein with six C 2 H 2 -type, C-terminal zinc finger motifs and is activated by provirus integration in T-cell lymphoma lines selected for interleukin-2 independence in culture and in primary retrovirus-induced thymomas. Gfi-1 expression in adult animals is restricted to the thymus, spleen, and testis and is enhanced in mitogen-stimulated splenocytes. In this report, we show that Gfi-1 is a 55-kDa nuclear protein that binds DNA in a sequence-specific manner. The Gfi-1 binding site, TAAATCAC(A/ T)GCA, was defined via random oligonucleotide selection utilizing a bacterially expressed glutathione S-transferase-Gfi-1 fusion protein. Binding to this site was confirmed by electrophoretic mobility shift assays and DNase I footprinting. Methylation interference analysis and electrophoretic mobility shift assays with mutant oligonucleotides defined the relative importance of specific bases at the consensus binding site. Deletion of individual zinc fingers demonstrated that only zinc fingers 3, 4, and 5 are required for sequence-specific DNA binding. Potential Gfi-1 binding sites were detected in a large number of eukaryotic promoter-enhancers, including the enhancers of several proto-oncogenes and cytokine genes and the enhancer of the human cytomegalovirus (HCMV) major immediate-early promoter, which contains two such sites. HCMV major immediate-early-chloramphenicol acetyltransferase reporter constructs, transfected into NIH 3T3 fibroblasts, were repressed by Gfi-1, and the repression was abrogated by mutation of critical residues in the two Gfi-1 binding sites. These results suggest that Gfi-1 may play a role in HCMV biology and may contribute to oncogenesis and T-cell activation by repressing the expression of genes that inhibit these processes.

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“…[4][5][6] It retains cis regulatory elements recognized by ubiquitous transcription factors including AP-1, 7 CREB, 8 NF-kB 9,10 and retinoic acid nuclear receptors (RARs). 11,12 Despite these properties, CMV-based expression cassettes show timelimited transcriptional activity which is usually silenced within a few days after their introduction in target cells 3,10 both in vitro and in vivo. This phenomenon has been recently associated with the production of cytokines, such as interferon-␥ (INF-␥), capable of suppressing transgene expression.…”

Section: Introductionmentioning

confidence: 99%

Transcriptionally active drugs improve adenovirus vector performance in vitro and in vivo

et al. 2000

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Retinoic acid receptors initiate induction of the cytomegalovirus enhancer in embryonal cells.

Cited by 59 publications

References 43 publications

Doxorubicin Enhances the Expression of Transgene Under Control of the CMV Promoter in Anaplastic Thyroid Carcinoma Cells

Doxorubicin Enhances the Expression of Transgene Under Control of the CMV Promoter in Anaplastic Thyroid Carcinoma Cells

Gfi-1 Encodes a Nuclear Zinc Finger Protein That Binds DNA and Functions as a Transcriptional Repressor

Transcriptionally active drugs improve adenovirus vector performance in vitro and in vivo

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