Abstract
Targeted drug delivery systems are special importance for developing gene therapeutic drugs that recognize and eliminate tumor cells. It is desirable that therapeutic genes be expressed predominantly in tumor cells after their targeted delivery into the tumor. Hence, the distribution of the expression product through various tissues should be studied when testing a therapeutic gene in vivo. The sodium iodide symporter (NIS) is attractive as a reporter because its tissue level is easy to quantify by noninvasive imaging methods. Therapeutic gene expression in tumor cells is achieved using various promoters, including strong nonspecific promoters; moderately active tissue-specific promoters; and tumor-specific promoters, which function in a broad range of tumor cells, but have low activity. The relationship between the promoter strength and reporter NIS activity is still unclear. The reporter gene was used to test three promoters types for activity in melanoma cells. The functional activity of NIS expressed from a cloned gene was compared for the three promoters types. Although the promoters greatly varied in strength, only minor changes were observed for NIS functional activity. A relatively weak melanoma-specific promoter ensured a high NIS activity in melanoma cells. Weaker tumorspecific promoters determined a high NIS activity only in some cells of the melanoma origin.
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References
Chung J.-K. 2002. Sodium iodide symporter: Its role in nuclear medicine. J. Nucl. Med. 43, 1188–1200.
Dohan O., Vieja A.D.E.L.A., Paroder V., et al. 2003. Regulation, and medical significance. Endocrine Rev. 24, 48–77.
Perron B., Rodriguez A.M., Leblanc G., Pourcher T. 2001. Cloning of the mouse sodium iodide symporter and its expression in the mammary gland and other tissues. J. Endocrinol. 170, 185–196.
Dai G., Levy O. 1996. Cloning and characterization of the thyroid iodide transporter. Nature. 379, 458–460.
Shimura H., Haraguchi K., Miyazaki A., et al. 1997. Iodide uptake and experimental 131I therapy in transplanted undifferentiated thyroid cancer cells expressing the Na+/I− symporter gene. Endocrinology. 138, 4493–4496.
Riesco-Eizaguirre G., Santisteban P. 2006. A perspective view of sodium iodide symporter research and its clinical implications. Eur. J. Endocrinol. 155, 495–512.
Baril P., Martin-Duque P., Vassaux G. 2010. Visualization of gene expression in the live subject using the Na/I symporter as a reporter gene: Applications in biotherapy. Br. J. Pharmacol. 159, 761–771.
Terrovitis J., Kwok K.F., Lautamäki R., et al. 2008. Ectopic expression of the sodium-iodide symporter enables imaging of transplanted cardiac stem cells in vivo by single-photon emission computed tomography or positron emission tomography. J. Am. Coll. Cardiol. 52, 1652–1660.
Barton K.N., Stricker H., Brown S.L., et al. 2008. Phase I study of noninvasive imaging of adenovirus-mediated gene expression in the human prostate. Mol. Ther. 16, 1761–1769.
Barton K.N., Stricker H., Elshaikh M.A., et al. 2011. Feasibility of adenovirus-mediated hNIS gene transfer and 131I radioiodine therapy as a definitive treatment for localized prostate cancer. Mol. Ther. 19, 1353–1359.
Riesco-Eizaguirre G., De la Vieja A., Rodriguez I., et al. 2011. Telomerase-driven expression of the sodium iodide symporter (NIS) for in vivo radioiodide treatment of cancer: a new broad-spectrum NIS-mediated antitumor approach. J. Clin. Endocrinol. Metab. 96, E1435–E1443.
Huang R., Zhao Z., Ma X., et al. 2011. Targeting of tumor radioiodine therapy by expression of the sodium iodide symporter under control of the survivin promoter. Cancer Gene Ther. 18, 144–152.
Chomczynski P., Sacchi N. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanatephenol-chloroform extraction. Anal. Biochem. 162, 156–159.
Weiss S.J., Philp N.J., Grollman E.F. 1984. Iodide transport in a continuous line of cultured cells from rat thyroid. Endocrinology. 114, 1090–1098.
Ambrosini G., Adida C., Sirugo G., Altieri D.C. 1998. Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting. J. Biol. Chem. 273, 11177–11182.
Yang L., Cao Z., Yan H., Wood W.C. 2003. Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: Implication for cancer specific therapy. Cancer Res. 63, 6815–6824.
Mityaev M.V., Kopantzev E.P., Buzdin A.A., et al. 2008. Functional significance of a putative sp1 transcription factor binding site in the survivin gene promoter. Biochemistry (Moscow). 73, 1183–1191.
Bao R., Connolly D.C., Murphy M., et al. 2002. Activation of cancer-specific gene expression by the survivin promoter. J. Natl. Cancer Inst. 94, 522–528.
Zhu Z.B., Makhija S.K., Lu B., et al. 2004. Transcriptional targeting of tumors with a novel tumor-specific survivin promoter. Cancer Gene Ther. 11, 256–262.
Konopka K., Spain C., Yen A., et al. 2009. Correlation between the levels of survivin and survivin promoter-driven gene expression in cancer and non-cancer cells. Cell. Mol. Biol. Lett. 14, 70–89.
Li F., Altieri D.C. 1999. The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression. Cancer Res. 59, 3143–3151.
Kyo S., Takakura M., Fujiwara T., Inoue M. 2008. Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers. Cancer Sci. 99, 1528–1538.
Gu J., Fang B. 2003. Telomerase promoter-driven cancer gene therapy. Cancer Biol. Ther. 2, S64–S70.
Kim S.H., Chung H.K., Kang J.H., et al. 2008. Tumortargeted radionuclide imaging and therapy based on human sodium iodide symporter gene driven by a modified telomerase reverse transcriptase promoter. Hum. Gene Ther. 19, 951–957.
Takakura M., Kyo S., Kanaya T., et al. 1999. Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res. 59, 551–557.
Davis J.J., Wang L., Dong F., et al. 2006. Oncolysis and suppression of tumor growth by a GFP-expressing oncolytic adenovirus controlled by an hTERT and CMV hybrid promoter. Cancer Gene Ther. 13, 720–723.
Wirth T., Zender L., Schulte B., et al. 2003. A telomerase-dependent conditionally replicating adenovirus for selective treatment of cancer. Cancer Res. 63, 3181–3188.
Hearing V.J., Tsukamoto K. 1991. Enzymatic control of pigmentation in mammals. FASEB J. 5, 2902–2909.
Van Groningen J.J., Bloemers H.P., Swart G.W. 1995. Identification of melanoma inhibitory activity and other differentially expressed messenger RNAs in human melanoma cell lines with different metastatic capacity by messenger RNA differential display. Cancer Res. 55, 6237–6243.
Perez R.P., Zhang P., Bosserhoff A.K., et al. 2000. Expression of melanoma inhibitory activity in melanoma and nonmelanoma tissue specimens. Hum. Pathol. 31, 1381–1388.
Hart I.R., Vile R.G. 1994. Targeted therapy for malignant melanoma. Curr. Opin. Oncol. 6, 221–225.
Pleshkan V.V., Alekseenko I.V., Zinovyeva M.V., et al. 2011. Promoters with cancer cell-specific activity for melanoma gene therapy. Acta Naturae. 3, 13–21.
Bosserhoff A.K., Kondo S., Moser M., et al. 1997. Mouse CD-RAP/MIA gene: Structure, chromosomal localization, and expression in cartilage and chondrosarcoma. Dev. Dynam. 208, 516–525.
Bosserhoff A.K., Kaufmann M., Kaluza B., et al. 1997. Melanoma-inhibiting activity, a novel serum marker for progression of malignant melanoma. Cancer Res. 57, 3149–3153.
Rothfels H., Paschen A., Schadendorf D. 2003. Evaluation of combined gene regulatory elements for transcriptional targeting of suicide gene expression to malignant melanoma. Exp. Dermatol. 12, 799–810.
Schoensiegel F., Paschen A., Sieger S., et al. 2004. MIA (melanoma inhibitory activity) promoter mediated tissue-specific suicide gene therapy of malignant melanoma. Cancer Gene Ther. 11, 408–418.
Mitrofanova E., Unfer R., Vahanian N., Link C., 2006. Rat sodium iodide symporter allows using lower dose of 131I for cancer therapy. Gene Ther. 13, 1052–1056.
Vadysirisack D., Shen D., Jhiang S. 2006. Correlation of Na+/I− symporter expression and activity: Implications of Na+/I− symporter as an imaging reporter gene. J. Nucl. Med. 47, 182–190.
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Original Russian Text © A.I. Kuzmich, E.P. Kopantsev, T.V. Vinogradova, E.D. Sverdlov, 2014, published in Molekulyarnaya Biologiya, 2014, Vol. 48, No. 1, pp. 142–152.
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Kuzmich, A.I., Kopantsev, E.P., Vinogradova, T.V. et al. Comparative activity of several promoters in driving NIS expression in melanoma cells. Mol Biol 48, 121–129 (2014). https://doi.org/10.1134/S0026893314010075
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DOI: https://doi.org/10.1134/S0026893314010075