Study on teratogenic effects of Methotrexate
- Study on teratogenic effects of Methotrexate; Alteration of Gene Expression pattern in Human Placenta Choriocarcinoma (JEG-3) Cells
- Alteration of Gene Expression pattern in Human Placenta Choriocarcinoma (JEG-3) Cells
- 이지나; 김연정; 류재천
- Methotrexate; Gene Expression pattern; JEG-3
- Issue Date
- BioChip Journal
- VOL 4, NO 3, 189-196
- Methotrexate is a well known chemotherapeutic
agent, extensively used for leukemia and other
cancers. Although its efficacy is wide, methotrexate
can cause serious or life-threatening toxicities on liver,
lungs, kidney, and immune system. Teratogenicity is
one of the methotrexate-induced side effects. So, we
performed with JEG-3, human placenta choriocarcinoma
cell line, to identify the differentially expressed
genes (DEGs) related to teratogenicity of methotrexate
using an Agilent 44-K whole human genome chip.
Through the analysis of gene expression profiles, we
identified 887 up-regulated genes and 828 down-regulated
genes above 1.5-fold by methotrexate. At IC30
doses recognized genes were functionally categorized
as being involved in purine and pyrimidine biosynthetic
process, cell cycle arrest, and apoptosis. Functionally
important purine and pyrimidine biosynthesis-related
genes were further validated by real-time RT-PCR.
The results showed that GART, HPRT1, TYMS, and
CTPS genes altered their expression levels by methotrexate.
Alteration of these genes may lead to methotrexate-
induced teratogenicity, which caused by imbalance
of nucleotide biosynthesis. In conclusion, both
gene expression profiles and functional analysis have
identified potential gene-based biomarkers and provided
insights into the mechanism underlying the response
of human placenta cell line to methotrexate exposure.
Keywords: Methotrexate, Teratogenicity, Nucleotide
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