Promoter Methylation and Methotrexate Resistance
Author Information
Author(s): Yang Rui, Li Wei-Wei, Hoang Bang H, Kim Hansoo, Banerjee Debabrata, Kheradpour Albert, Healey John H, Meyers Paul A, Bertino Joseph R, Gorlick Richard
Primary Institution: The Albert Einstein College of Medicine
Hypothesis
Is promoter methylation a mechanism for reduced folate carrier (RFC) transcription regulation and methotrexate resistance in malignant cell lines?
Conclusion
Promoter methylation is a potential basis for methotrexate resistance, as indicated by the correlation between methylation levels and RFC mRNA expression.
Supporting Evidence
- A reverse correlation (correlation coefficient = -0.59) was identified between the promoter methylation and RFC mRNA levels.
- Heavy promoter methylation was previously identified as a basis for the complete silencing of RFC in MDA-MB-231 breast cancer cells.
- Partial promoter methylation and RFC mRNA down-regulation were observed in the M805 cell line.
Takeaway
This study found that when certain cancer cells have a lot of a chemical called methylation on their DNA, they don't make a protein that helps them take in a medicine called methotrexate, which can make it harder to treat their cancer.
Methodology
The study used methylation specific PCR and quantitative real-time RT-PCR to assess RFC promoter methylation and mRNA levels in a panel of malignant cell lines.
Limitations
The study primarily focused on a limited number of cell lines and may not represent all tumor types.
Statistical Information
P-Value
<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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