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Altered gene expression profiles by sodium/iodide symporter gene transfection in a human anaplastic thyroid carcinoma
Jae Gol Choe1, Yu-Ri Kim, Ki-Nam Kim
1Department of Nuclear Medicine, Korea University Medical School, Seoul, South Korea.
Background:
The sodium/iodide symporter (NIS) is a membrane glycoprotein that mediates active 131I uptake during the treatment of cancer of the thyroid gland and extrathyroidal tissues. NIS gene transfection, a gene-therapy modality, has been introduced in many types of cancer, such as prostate cancer and breast cancer, and has demonstrated a high potential for the treatment of non-thyroidal cancers.
Aim:
To investigate the pattern of NIS gene expression and provide evidence of its beneficial effects in human anaplastic cancer ARO cells by using a radioactive complementary DNA (cDNA) microarray.
Methods:
For cDNA microarray data analysis, superimposed images and clustergrams were prepared from basic radioactivity data obtained using a phosphoimager system. Gene expression profiles were constructed using the Z-transformed values of genes related to cancer biology.
Results:
Radioactive cDNA microarray studies showed that 11 genes were upregulated (Z ratio > 1.5) and 31 genes were downregulated (Z ratio < -1.5) in response to NIS gene transfection. Of these differentially expressed genes, 33% were related to cell proliferation and apoptosis. Moreover, NIS gene transfection into an anaplastic thyroid cancer cell line affected the expression of the protein tyrosine phosphatase (PTP) family and Ras oncogene family, including Ras, Rac and Rab.
Conclusion:
The identification of changes in the patterns of gene expression may provide a better understanding of the response of molecular mechanisms to NIS gene transfection.
Insights
Sodium/iodide symporter (NIS) gene therapy shows promise for non-thyroidal cancers. Transfection altered gene expression, affecting cell proliferation and apoptosis pathways in anaplastic thyroid cancer cells.
Area of Science:
- Molecular Biology
- Cancer Genetics
- Gene Therapy
Background:
- The sodium/iodide symporter (NIS) facilitates radioactive iodine uptake, crucial for thyroid cancer treatment.
- NIS gene therapy is being explored for various cancers, including prostate and breast cancer, showing therapeutic potential.
Purpose of the Study:
- To analyze NIS gene expression patterns in human anaplastic cancer ARO cells.
- To evaluate the therapeutic effects of NIS gene transfection using radioactive complementary DNA (cDNA) microarray.
Main Methods:
- Radioactive cDNA microarray analysis of gene expression profiles.
- Construction of gene expression profiles using Z-transformed values for cancer-related genes.
Main Results:
- NIS gene transfection led to 11 upregulated and 31 downregulated genes.
- Thirty-three percent of affected genes were linked to cell proliferation and apoptosis.
- Expression of protein tyrosine phosphatase (PTP) and Ras oncogene families was impacted.
Conclusions:
- Changes in gene expression patterns offer insights into molecular responses to NIS gene therapy.
- Understanding these mechanisms can enhance the application of NIS gene therapy in non-thyroidal cancers.
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