Methylation of WTH3, a possible drug resistant gene, inhibits p53 regulated expression
2008

WTH3 Gene's Role in Drug Resistance and p53 Interaction

publication Evidence: moderate

Author Information

Author(s): Tian Kegui, Wang Yuezeng, Huang Yu, Sun Boqiao, Li Yuxin, Xu Haopeng

Primary Institution: State University of New York at Stony Brook

Hypothesis

Does the methylation of the WTH3 gene affect its expression and contribute to drug resistance in cancer cells?

Conclusion

The study shows that WTH3 is crucial in the development of multidrug resistance and that DNA methylation negatively impacts its expression regulated by p53.

Supporting Evidence

  • Over-expression of WTH3 in drug-resistant cells reduced MDR1 gene expression.
  • WTH3 promoter was hypermethylated in drug-resistant breast cancer cells.
  • Knockdown of WTH3 increased resistance to Doxorubicin in HEK293 cells.
  • DNA methylation negatively affected p53's ability to activate WTH3 expression.

Takeaway

The WTH3 gene helps cancer cells resist drugs, and when it is turned off by a process called methylation, it makes it harder for a protein called p53 to help fight cancer.

Methodology

The study used shRNA to knock down WTH3 expression in HEK293 cells and examined the effects of DNA methylation on p53's regulation of WTH3.

Digital Object Identifier (DOI)

10.1186/1471-2407-8-327

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