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Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase
Racheli Erez-Roman1, Reut Pienik, Anthony H Futerman
1Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
Abstract:
Intervention in the ceramide metabolic pathway is emerging as a novel means to regulate cancer and to modify the activity of chemotherapeutic drugs. We now study mRNA expression levels of the six ceramide synthase (CerS) genes in breast cancer tissue. CerS2 and CerS6 mRNA was significantly elevated in breast cancer tissue compared to paired normal tissue, with approximately half of the individuals showing elevated CerS2 and CerS6 mRNA. A significant correlation was found between CerS2 and CerS6 expression, and between CerS4 and CerS2/CerS6 expression. Moreover, patients that expressed higher CerS2 or 4 mRNA levels tended to show no changes in sphingosine kinase 1 levels, and likewise patients that expressed no change in CerS2 or CerS4 mRNA levels tended to express higher levels of sphingosine kinase 1. Together these results suggest an important role for the CerS genes in breast cancer etiology or diagnosis.
Insights
Altering ceramide metabolism, specifically ceramide synthase (CerS) genes, shows promise in cancer treatment. Elevated CerS2 and CerS6 mRNA in breast cancer suggests their role in disease development and potential as diagnostic markers.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- The ceramide metabolic pathway is a novel target for cancer therapy and drug modification.
- Ceramide synthase (CerS) genes play a critical role in regulating ceramide levels.
Purpose of the Study:
- To investigate the mRNA expression levels of the six ceramide synthase (CerS) genes in breast cancer tissue.
- To explore the correlation between CerS gene expression and sphingosine kinase 1 levels in breast cancer patients.
Main Methods:
- Quantitative analysis of mRNA expression levels for six CerS genes in breast cancer and paired normal tissues.
- Statistical analysis to determine correlations between CerS gene expression and clinical parameters.
Main Results:
- CerS2 and CerS6 mRNA levels were significantly elevated in breast cancer tissues compared to normal tissues.
- A significant positive correlation was observed between CerS2 and CerS6 expression, and between CerS4 and CerS2/CerS6 expression.
- Inverse relationships were noted between CerS2/CerS4 mRNA levels and sphingosine kinase 1 levels.
Conclusions:
- The study suggests a significant role for CerS genes in the etiology or diagnosis of breast cancer.
- Elevated CerS2 and CerS6 expression may serve as potential biomarkers for breast cancer.
- The interplay between CerS genes and sphingosine kinase 1 warrants further investigation in cancer therapeutics.