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Expression profiling of tumor necrosis factor alpha-induced apoptosis-associated genes in human solid tumor cell
Yoshiaki Yanai1, Mark J Micallef, Shigeto Yamamoto
1Hayashibara Biochemical Laboratories Inc., Fujisaki Institute, Fujisaki 675-1, Okayama 702-8006, Japan.
Background:
The induction of genes associated with cellular apoptosis by tumor necrosis factor-alpha (TNF-alpha) in human cancer cell line sof various tissue origins may characterize TNF-alpha responder cell lines/cancers.
Materials And Methods:
Using quantitative real-time polymerase chain reaction (PCR), the comprehensive molecular profiling of genes downstream of the TNF-alpha receptor genes in 91 well-defined human cancer cell lines allowed us to elucidate relationships between TNF-alpha response and the genetic expression profiles of the target cell lines.
Results:
Among the 52 genes tested, the above average expression of Akt mRNA showed significant correlation with TNF-alpha-induced susceptibility to apoptosis. In addition, multidrug resistance protein 5 (MRP5) and tumor necrosis factor receptor type 1 (TNFR1) mRNA expressions also appear to be possible markers for responsiveness to TNF-alpha.
Conclusion:
These results provide a preliminary basis for the screening for genetic markers that may help to predict a favorable therapeutic outcome, and also to identify patients who may benefit from cytokine therapy.
Insights
Tumor necrosis factor-alpha (TNF-alpha) can induce apoptosis in cancer cells. Akt mRNA expression levels may predict which cancer cell lines respond to TNF-alpha, aiding in targeted therapy selection.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tumor necrosis factor-alpha (TNF-alpha) induces apoptosis in human cancer cell lines.
- Identifying TNF-alpha responder cell lines is crucial for cancer therapy.
- TNF-alpha response is linked to specific genetic expression profiles.
Purpose of the Study:
- To elucidate relationships between TNF-alpha response and gene expression profiles.
- To identify potential genetic markers for predicting TNF-alpha responsiveness.
- To explore the role of gene expression in TNF-alpha-induced apoptosis.
Main Methods:
- Quantitative real-time polymerase chain reaction (PCR) was employed.
- Comprehensive molecular profiling of 91 human cancer cell lines was performed.
- Gene expression downstream of TNF-alpha receptor genes was analyzed.
Main Results:
- Above-average Akt mRNA expression correlated significantly with TNF-alpha-induced apoptosis susceptibility.
- Multidrug resistance protein 5 (MRP5) mRNA expression may indicate TNF-alpha responsiveness.
- Tumor necrosis factor receptor type 1 (TNFR1) mRNA expression is a potential marker for TNF-alpha responsiveness.
Conclusions:
- Genetic markers can predict favorable therapeutic outcomes in cancer patients.
- Identifying patients who benefit from cytokine therapy is possible.
- This study provides a preliminary basis for screening predictive genetic markers.