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Published on: April 5, 2015
Global gene expression of fission yeast in response to cisplatin
1Istituto Nazionale Tumori, 20133, Milan, Italy.
Abstract:
The cellular response to the antitumor drug cisplatin is complex, and resistance is widespread. To gain insights into the global transcriptional response and mechanisms of resistance, we used microarrays to examine the fission yeast cell response to cisplatin. In two isogenic strains with differing drug sensitivity, cisplatin activated a stress response involving glutathione-S-transferase, heat shock, and recombinational repair genes. Genes required for proteasome-mediated protein degradation were up-regulated in the sensitive strain, whereas genes for DNA damage recognition/repair and for mitotic progression were induced in the resistant strain. The response to cisplatin overlaps in part with the responses to cadmium and the DNA-damaging agent methylmethane sulfonate. The different gene groups involved in the cellular response to cisplatin help the cells to tolerate and repair DNA damage and to overcome cell cycle blocks. These findings are discussed with respect to known cisplatin response pathways in human cells.
Insights
This study reveals how yeast cells respond to cisplatin, identifying key genes involved in stress, DNA repair, and resistance. Understanding these cellular mechanisms can inform cancer drug development.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Cisplatin is a vital antitumor drug, but its efficacy is limited by widespread cellular resistance.
- Understanding the global transcriptional response to cisplatin is crucial for developing strategies to overcome drug resistance.
Purpose of the Study:
- To investigate the global transcriptional response of fission yeast to cisplatin.
- To identify genes and pathways involved in cisplatin sensitivity and resistance.
Main Methods:
- Microarray analysis was employed to examine gene expression profiles in isogenic fission yeast strains with differential cisplatin sensitivity.
- Comparative analysis of gene expression patterns between sensitive and resistant strains.
Main Results:
- Cisplatin induced a conserved stress response, including genes for glutathione-S-transferase, heat shock, and recombinational repair.
- Sensitive cells upregulated genes for proteasome-mediated protein degradation.
- Resistant cells induced genes involved in DNA damage recognition/repair and mitotic progression.
- The transcriptional response to cisplatin partially overlaps with responses to cadmium and methylmethane sulfonate.
Conclusions:
- Fission yeast mounts a complex transcriptional response to cisplatin, involving DNA repair, stress response, and cell cycle regulation.
- Distinct gene expression patterns in sensitive and resistant strains highlight specific mechanisms contributing to cisplatin tolerance and resistance.
- These findings provide insights into conserved cisplatin response pathways relevant to human cells.
