The glial fibrillary acidic protein promoter directs sodium/iodide symporter gene expression for radioiodine therapy of malignant glioma

Li,Wei; Tan,Jian; Wang,Peng; Li,Ning; Zhang,Fuhai

doi:10.3892/ol.2012.1055

The glial fibrillary acidic protein promoter directs sodium/iodide symporter gene expression for radioiodine therapy of malignant glioma

Authors:
- Wei Li
- Jian Tan
- Peng Wang
- Ning Li
- Fuhai Zhang
View Affiliations

Affiliations: Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, P.R. China
Published online on: December 3, 2012 https://doi.org/10.3892/ol.2012.1055
Pages: 669-674

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Radioiodine is a routine therapy for differentiated thyroid cancers. Non‑thyroid cancers may be treated with radioiodine following transfection with the human sodium/iodide symporter (hNIS) gene. The glial fibrillary acidic protein (GFAP) promoter is an effective tumor‑specific promoter for gene expression and thus may be useful in targeted gene therapy of malignant glioma. The present study used GFAP promoter‑modulated expression of the hNIS gene in an experimental model of radioiodine‑based treatment for malignant glioma. Cells were transfected using a recombination adenovirus and evaluated in cells by studying the transfected transgene expression through western blot analysis, 125I uptake and efflux, clonogenicity following 131I treatment and radioiodine therapy using a U87 xenograft nude mouse model. Following transfection with the hNIS gene, the cells showed 95‑70‑fold higher 125I uptake compared with the control cells transfected with Ad‑cytomegalovirus (CMV)‑enhanced green fluorescent protein (EGFP). The western blotting revealed bands of ~70, 49 and 43 kDa, consistent with the hNIS, GFAP and β‑actin proteins. The clonogenic assay indicated that, following exposure to 500 µCi of 131I‑iodide for 12 h, >90% of cells transfected with the hNIS gene were killed. Ad‑GFAP‑hNIS-transfected and 2 mCi 131I-injected U87 xenograft nude mice survived the longest of the three groups. The hNIS‑expressing tumor tissue accumulated 99mTcO4 rapidly within 30 min of it being intraperitoneally injected. The experiments demonstrated that effective 131I therapy was achieved in the malignant glioma cell lines following the induction of tumor‑specific iodide uptake activity by GFAP promoter‑directed hNIS gene expression in vitro and in vivo. 131I therapy retarded Ad‑GFAP‑hNIS transfected‑tumor growth following injection with 131I in U87 xenograft‑bearing nude mice.

View Figures

View References

1.	Vredenburgh JJ, Desjardins A, Reardon DA and Friedman HS: Experience with irinotecan for the treatment of malignant glioma. Neuro Oncol. 11:80–91. 2009. View Article : Google Scholar : PubMed/NCBI
2.	Li W, Tan J, Wang P and Wu P: Cotransfected sodium iodide symporter and human tyroperoxidase genes following human telomerase reverse transcriptase promoter for targeted radio-iodine therapy of malignant glioma cells. Cancer Biother Radiopharm. 26:443–451. 2011. View Article : Google Scholar
3.	Gu J, Kagawa S, Takakura M, Kyo S, Inoue M, Roth JA and Fang B: Tumor-specific transgene expression from the human telomerase reverse transcriptase promoter enables targeting of the therapeutic effects of the Bax gene to cancers. Cancer Res. 60:5359–5364. 2000.
4.	Brenner M, Kisseberth WC, Su Y, Besnard F and Messing A: GFAP promoter directs astrocyte-specific expression in transgenic mice. J Neurosci. 14:1030–1037. 1994.PubMed/NCBI
5.	Nolte C, Matyash M, Pivneva T, Schipke CG, Ohlemeyer C, Hanisch UK, Kirchhoff F and Kettenmann H: GFAP promoter-controlled EGFP-expressing transgenic mice: a tool to visualize astrocytes and astrogliosis in living brain tissue. Glia. 33:72–86. 2001. View Article : Google Scholar : PubMed/NCBI
6.	Besnard F, Brenner M, Nakatani Y, Chao R, Purohit HJ and Freese E: Multiple interacting sites regulate astrocyte-specific transcription of the human gene for glial fibrillary acidic protein. J Biol Chem. 266:18877–18883. 1991.
7.	Yang N and Mahato RI: GFAP promoter-driven RNA interference on TGF-β1 to treat liver fibrosis. Pharm Res. 28:752–761. 2011.PubMed/NCBI
8.	Giralt A, Friedman HC, Caneda-Ferrón B, Urban N, Moreno E, Rubio N, Blanco J, Peterson A, Canals JM and Alberch J: BDNF regulation under GFAP promoter provides engineered astrocytes as a new approach for long-term protection in Huntington’s disease. Gene Ther. 17:1294–1308. 2010.PubMed/NCBI
9.	Huang J, Gao J, Lv X, Li G, Hao D, Yao X, Zhou L, Liu D and Wang R: Target gene therapy of glioma: overexpression of BAX gene under the control of both tissue-specific promoter and hypoxia-inducible element. Acta Biochim Biophys Sin (Shanghai). 42:274–280. 2010. View Article : Google Scholar : PubMed/NCBI
10.	Hede SM, Hansson I, Afink GB, Eriksson A, Nazarenko I, Andrae J, Genove G, Westermark B and Nistér M: GFAP promoter driven transgenic expression of PDGFB in the mouse brain leads to glioblastoma in a Trp53 null background. Glia. 57:1143–1153. 2009. View Article : Google Scholar : PubMed/NCBI
11.	Chen L, Altmann A, Mier W, Eskerski H, Leotta K, Guo L, Zhu R and Haberkorn U: Radioiodine therapy of hepatoma using targeted transfer of the human sodium/iodide symporter gene. J Nucl Med. 47:854–862. 2006.PubMed/NCBI
12.	Spitzweg C, Zhang S, Bergert ER, Castro MR, McIver B, Heufelder AE, Tindall DJ, Young CY and Morris JC: Prostate-specific antigen (PSA) promoter-driven androgen-inducible expression of sodium iodide symporter in prostate cancer cell lines. Cancer Res. 59:2136–2141. 1999.PubMed/NCBI
13.	Boland A, Ricard M, Opolon P, Bidart J, Yeh P, Filetti S, Schlumberger M and Perricaudet M: Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy. Cancer Res. 60:3484–3492. 2000.PubMed/NCBI
14.	Schipper M, Weber A, Béhé M, Göke R, Joba W, Schmidt H, Bert T, Simon B, Arnold R, Heufelder A and Behr T: Radioiodide treatment after sodium iodide symporter gene transfer is a highly effective therapy in neuroendocrine tumor cells. Cancer Res. 63:1333–1338. 2003.PubMed/NCBI
15.	Ma XJ, Huang R and Kuang AR: AFP promoter enhancer increased specific expression of the human sodium iodide symporter (hNIS) for targeted radioiodine therapy of hepato-cellular carcinoma. Cancer Invest. 27:673–681. 2009. View Article : Google Scholar
16.	Scholz IV, Cengic N, Baker CH, Harrington KJ, Maletz K, Bergert ER, Vile R, Göke B, Morris JC and Spitzweg C: Radioiodine therapy of colon cancer following tissue-specific sodium iodide symporter gene transfer. Gene Ther. 12:272–280. 2005. View Article : Google Scholar : PubMed/NCBI
17.	Spitzweg C, Baker CH, Bergert ER, O’Connor MK and Morris JC: Image-guided radioiodide therapy of medullary thyroid cancer after carcinoembryonic antigen promoter-targeted sodium iodide symporter gene expression. Hum Gene Ther. 18:916–924. 2007. View Article : Google Scholar
18.	Kim HJ, Jeon YH, Kang JH, Lee YJ, Kim KI, Chung HK, Jeong JM, Lee DS, Lee MC and Chung JK: In vivo long-term imaging and radioiodine therapy by sodium-iodide symporter gene expression using a lentiviral system containing ubiquitin C promoter. Cancer Biol Ther. 6:1130–1135. 2007. View Article : Google Scholar : PubMed/NCBI
19.	Sieger S, Jiang S, Schönsiegel F, Eskerski H, Kübler W, Altmann A and Haberkorn U: Tumour-specific activation of the sodium/iodide symporter gene under control of the glucose transporter gene 1 promoter (GTI-1.3). Eur J Nucl Med Mol Imaging. 30:748–756. 2003. View Article : Google Scholar : PubMed/NCBI
20.	Doloff JC, Jounaidi Y and Waxman DJ: Dual E1A oncolytic adenovirus: targeting tumor heterogeneity with two independent cancer-specific promoter elements, DF3/MUC1 and hTERT. Cancer Gene Ther. 18:153–166. 2011. View Article : Google Scholar : PubMed/NCBI
21.	Löw K, Blesch A, Herrmann J and Tuszynski MH: A dual promoter lentiviral vector for the in vivo evaluation of gene therapeutic approaches to axon regeneration after spinal cord injury. Gene Ther. 17:577–591. 2010.PubMed/NCBI