Document Detail


Enhanced expression of adenovirus-mediated sodium iodide symporter gene in MCF-7 breast cancer cells with retinoic acid treatment.
MedLine Citation:
PMID:  17332617     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increased expression of the sodium iodide symporter (NIS) is required for effective radioiodine treatment and reporter gene imaging of breast cancer. We investigated the effect of retinoic acid on adenovirus-mediated expression of the human NIS gene in the MCF-7 breast cancer cell line. METHODS: The MCF-7 cell line was infected with recombinant adenovirus carrying the human NIS gene (Rad-NIS). Levels of NIS messenger RNA (mRNA) and protein expression and radioiodine ((125)I) uptake were measured to evaluate adenovirus-mediated NIS gene expression in wild-type and Rad-NIS-infected MCF-7 cells after treatment with all-trans-retinoic acid (ATRA; 10(-8)-10(-6) mol/L). RESULTS: The transduction efficiency of adenovirus in MCF-7 cells at a multiplicity of infection (MOI) of 50 was >60%. After incubation with 10(-6) mol/L ATRA, the mRNA level in Rad-NIS-infected MCF-7 cells increased to 118.5 times that of wild-type MCF-7 cells, whereas the mRNA level in wild-type MCF-7 cells showed only a 2.1-fold increase. Western blot, immunocytochemical staining, and flow cytometry analyses showed that NIS protein expression in MCF-7 cells infected with Rad-NIS increased after ATRA treatment. With ATRA treatment, the amount of (125)I uptake increased in a dose-dependent manner (P < 0.001). The (125)I uptake in wild-type MCF-7 cells increased 3.1-, 5.5-, and 7.6-fold with treatment with 10(-8), 10(-7), and 10(-6) mol/L ATRA, respectively. Rad-NIS-infected cells showed a 4.0-fold increase in (125)I uptake. Treatment of Rad-NIS-infected cells with 10(-8), 10(-7), and 10(-6) mol/L ATRA increased (125)I uptake by 4.9-, 8.2-, and 27.6-fold, respectively, compared with wild-type MCF-7 cells. The level of NIS expression in Rad-NIS-infected MCF-7 cells treated with 10(-6) mol/L ATRA (245.0 +/- 13.7 pmol/10(6) cells) was much greater than the sum of the expression levels seen in ATRA-treated wild-type cells and Rad-NIS-infected wild-type cells. CONCLUSION: Retinoic acid increases adenovirus-mediated NIS expression in MCF-7 cells. Our results indicate that improved efficiency of NIS gene therapy or reporter imaging in breast cancer may be possible with retinoic acid treatment.
Authors:
Soo Jeong Lim; Jin Chul Paeng; Sung Jin Kim; Sang Yoon Kim; Heuiran Lee; Dae Hyuk Moon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of nuclear medicine : official publication, Society of Nuclear Medicine     Volume:  48     ISSN:  0161-5505     ISO Abbreviation:  J. Nucl. Med.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-02     Completed Date:  2007-04-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217410     Medline TA:  J Nucl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  398-404     Citation Subset:  IM    
Affiliation:
Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*
Breast Neoplasms / metabolism*,  pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Female
Gene Therapy
Gene Transfer, Horizontal
Humans
Iodine Radioisotopes / pharmacokinetics
Receptors, Retinoic Acid / physiology
Retinoid X Receptors / physiology
Symporters / genetics*
Tretinoin / pharmacology*
Chemical
Reg. No./Substance:
0/Iodine Radioisotopes; 0/Receptors, Retinoic Acid; 0/Retinoid X Receptors; 0/Symporters; 0/sodium-iodide symporter; 302-79-4/Tretinoin

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