Subscribe to RSS
DOI: 10.1055/s-2001-11020
© Johann Ambrosius Barth
Approaches to gene therapy with sodium/iodide symporter
Publication History
Publication Date:
31 December 2001 (online)

Summary:
Since cloning and characterization of the sodium iodide symporter (NIS) gene, several investigators explored the possibility of a novel cytoreductive gene therapy strategy based on NIS gene transfer into non-thyroidal tumor cells followed by radioiodine therapy. NIS gene transfer has been shown to be capable of inducing radioiodine accumulation in vitro and in vivo in several non-thyroidal cancer cell lines. Following PSA promoter-mediated NIS gene delivery we were able to demonstrate prostate-specific iodide accumulation in prostate cancer cells that was high enough to elicit a therapeutic response of 131-I in vitro and in vivo. This study clearly demonstrates the potential of NIS as a novel therapeutic gene for non-thyroidal cancers, in particular prostate cancer.
Key words:
Sodium/iodide symporter (NIS) - gene therapy - prostate cancer
References
- 1 Boland A, Ricard M, Opolon P, Bidart J-M, Yeh P, Filetti S, Schlumberger M, Perricaudet M. Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy. Cancer Res. 60 3484-3492 2000;
- 2 Cho J-Y, Xing S, Liu X, Buckwalter T LF, Hwa L, Sferra T J, Chiu I-M, Jhiang S M. Expression and activity of human Na+/I- symporter in human glioma cells by adenovirus-mediated gene delivery. Gene Ther. 7 740-749 2000;
- 3 Cleutjens K BJM, van der Korput H AGM, Ehren-van-Eekelen C C, Sikes R A, Fasciana C, Chung L W, Trapman J. A 6-kb promoter fragment mimics in transgenic mice the prostate-specific and androgen-regulated expression of the endogenous prostate-specific antigen gene in humans. Mol Endocrinol. 11 1256-1265 1997;
- 4 Dai G, Levy O, Carrasco N. Cloning and characterization of the thyroid iodide transporter. Nature. 379 458-460 1996;
- 5 De la Vieja A, Dohan O, Levy O, Carrasco N. Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology. Physiol Rev. 80 1083-1105 2000;
- 6 Mandell R B, Mandell L Z, Link C J. Radioisotope concentrator gene therapy using the sodium/iodide symporter gene. Cancer Res. 59 661-668 1999;
- 7 Mazzaferri E L. Carcinoma of follicular epithelium: Radioiodine and other treatments and outcomes. In: Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text. 7th ed. Philadelphia: Lippincott - Raven 922-945 1996
- 8 Shimura H, Haraguchi K, Miyazaki A, Endo T, Onaya T. Iodide uptake and experimental 131I therapy in transplanted undifferentiated thyroid cancer cells expressing the Na+/I- symporter gene. Endocrinology. 138 4493-4496 1997;
- 9 Smanik P A, Liu Q, Furminger T L, Ryu K, Xing S, Mazzaferri E L, Jhiang S M. Cloning of the human sodium iodide symporter. Biochem Biophys Res Commun. 226 339-345 1996;
- 10 Spitzweg C, O'Connor M K, Bergert E R, Tindall D J, Young C YF, Morris J C. Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter. Cancer Res . 60 6526-6530 2000;
- 11 Spitzweg C, Zhang S, Bergert E R, Castro M R, McIver B, Tindall D J, Young C YF, Morris J C. Prostate-specific antigen (PSA) promoter-driven androgen-inducible expression of sodium iodide symporter in prostate cancer cell lines. Cancer Res. 59 2136-2141 1999;
- 12 Stearns M E, McGarvey T. Prostate cancer: therapeutic, diagnostic, and basic studies. Lab Invest. 67 540-552 1992;
Christine SpitzwegM.D.
Mayo Clinic
Endocrine Research Unit
Guggenheim 625 200 First Street SW
Rochester, MN 55905
USA
Phone: 507-284-2324
Fax: 507-284-4521
Email: spitzweg.christine@mayo.edu