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The DCC gene suppresses the malignant phenotype of transformed human epithelial cells
A J Klingelhutz1, L Hedrick, K R Cho
1Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Abstract:
Loss of heterozygosity and loss of expression of the deleted in colon cancer (DCC) gene is frequently observed in a number of different cancer types. To determine if the DCC gene plays a direct role in tumor suppression, wild-type full-length or truncated DCC cDNA constructs were transfected into nitrosomethylurea (NMU) transformed tumorigenic HPV-immortalized human epithelial cells that had allelic loss and reduced expression of DCC. Full-length DCC suppressed tumorigenicity whereas truncated DCC did not. Tumorigenic reversion of initially suppressed transfectants was associated with loss of DCC expression and loss or rearrangement of transfected DCC sequences. These results provide the first direct evidence that DCC is a tumor suppressor gene.
Insights
The deleted in colon cancer (DCC) gene acts as a tumor suppressor. Restoring DCC gene expression in cancer cells inhibited tumor growth, providing direct evidence of its tumor-suppressive function.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Loss of heterozygosity and expression of the deleted in colon cancer (DCC) gene is common in various cancers.
- The precise role of DCC in tumor suppression remains unclear.
Purpose of the Study:
- To investigate the direct role of the DCC gene in tumor suppression.
- To determine if DCC gene restoration can inhibit cancer cell tumorigenicity.
Main Methods:
- Transfection of full-length or truncated DCC cDNA into NMU-transformed, tumorigenic human epithelial cells with existing DCC loss.
- Assessment of tumor suppression and tumorigenic reversion in transfected cells.
Main Results:
- Full-length DCC suppressed tumor formation in cancer cells.
- Truncated DCC failed to suppress tumorigenicity.
- Loss or rearrangement of DCC sequences correlated with the re-emergence of tumors.
Conclusions:
- These findings provide the first direct evidence that DCC is a tumor suppressor gene.
- DCC gene expression is critical for its tumor-suppressive function.