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Involvement of Myc targets in c-myc and N-myc induced human tumors
T Ben-Yosef1, O Yanuka, D Halle
1Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Givat-Ram, Israel.
Abstract:
The myc proto-oncogenes are transcription factors that directly regulate the expression of other genes, by binding to the specific DNA sequence, CACGTG. Among the target genes for c-Myc regulation are ECA39, p53, ornithine decarboxylase (ODC), alpha-prothymosin and Cdc25A. In this study we examined the involvement of c-Myc target genes in human oncogenesis induced by c-myc or N-myc. In MCF-7 breast cancer cells, the induction of c-myc expression by estrogen was followed by the induction of all the Myc targets that we examined, indicating that those genes can serve as c-Myc targets in human oncogenesis. Moreover, in breast tumors exhibiting c-myc overexpression, several Myc targets were also overexpressed. A clear correlation between the expression of c-myc and its targets was also detected in Burkitt's lymphomas, which involve a specific translocation of c-myc gene, but not in other lymphoma cells. Yet, in cells derived from a neuronal origin the pattern of expression of Myc targets was more complex. In a neuroepithelioma cell line that overexpresses c-myc, only some targets were expressed. In addition in neuroblastomas, in which N-myc is amplified and overexpressed, only ODC was overexpressed in all cell lines, while all other target genes were expressed in only some of the cell lines. The more complex expression pattern found for the Myc targets in neuroblastomas suggests that genes that were identified originally as targets for c-Myc regulation may be regulated by N-Myc, but other cell specific factors are also needed for transcription of the target genes.
Insights
Myc proto-oncogenes regulate gene expression, impacting human oncogenesis. This study shows Myc target genes are involved in breast cancer and lymphomas, with complex regulation in neuronal cancers.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Myc proto-oncogenes are transcription factors binding to CACGTG DNA sequences.
- Key c-Myc target genes include ECA39, p53, ornithine decarboxylase (ODC), alpha-prothymosin, and Cdc25A.
- Myc gene family members (c-Myc, N-Myc) are implicated in various human cancers.
Purpose of the Study:
- To investigate the role of c-Myc target genes in human oncogenesis driven by c-myc or N-myc.
- To determine if Myc target gene expression correlates with Myc overexpression in different cancer types.
Main Methods:
- Analysis of c-Myc and its target gene expression in MCF-7 breast cancer cells after estrogen induction.
- Examination of Myc target gene expression in human breast tumors with c-myc overexpression.
- Correlation analysis of c-myc and target gene expression in Burkitt's lymphomas and other lymphoma cells.
- Investigation of Myc target gene expression patterns in neuroepithelioma and neuroblastoma cell lines.
Main Results:
- Estrogen-induced c-myc expression in MCF-7 cells led to the induction of all examined Myc targets.
- Overexpression of c-myc in breast tumors correlated with the overexpression of several Myc target genes.
- A strong correlation between c-myc and its targets was observed in Burkitt's lymphomas but not other lymphomas.
- Neuronal-derived cells showed complex Myc target gene expression patterns; N-Myc overexpression in neuroblastomas primarily correlated with ODC overexpression.
Conclusions:
- Myc target genes play a role in human oncogenesis, particularly in breast cancer and specific lymphomas.
- Regulation of Myc target genes by N-Myc in neuronal cancers is suggested but appears to require additional cell-specific factors.
- The study highlights differential regulation of Myc targets depending on the Myc family member and cellular context.