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Human chromosomal localization, tissue/tumor expression, and regulatory function of the ets family gene EHF
L A Kleinbaum1, C Duggan, E Ferreira
1Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, 55455-0217, USA.
Abstract:
Ets factors are members of an ancient multigene family of transcription factors including oncoproteins and possibly tumor suppressors. We previously characterized a novel divergent ets gene, Ehf (ets homologous factor) in mice. Here we report the cDNA sequence, chromosomal location, and tissue/tumor expression patterns of the human EHF gene and the regulatory activity of the EHF protein. EHF maps to 11p12, which is deleted in many prostate, breast, and lung carcinomas and is a hot spot for inherited deletion- or amplification-associated developmental defects. EHF is differentially expressed in normal tissues and carcinomas and between tumor stages and is most highly expressed in the organs known to form carcinomas upon 11p12 deletion. EHF protein represses the ETS-2 induced activity of both stromelysin-1 and collagenase-1 promoters. These data suggest that EHF may contribute to human development and carcinogenesis and is a candidate for the 11p12 tumor suppressor gene.
Insights
The human EHF gene, located on chromosome 11p12, shows altered expression in various carcinomas. EHF protein may act as a tumor suppressor, potentially influencing human development and cancer.
Area of Science:
- Genetics
- Molecular Biology
- Oncology
Background:
- Ets factors are a multigene family of transcription factors with roles in cell regulation.
- The ets homologous factor (EHF) is a novel divergent ets gene previously identified in mice.
- The EHF gene's role in human development and carcinogenesis is not fully understood.
Purpose of the Study:
- To characterize the human EHF gene, including its cDNA sequence, chromosomal location, and expression patterns.
- To investigate the regulatory activity of the EHF protein.
- To evaluate EHF as a potential tumor suppressor gene associated with chromosome 11p12 deletions.
Main Methods:
- Human EHF gene sequencing and chromosomal mapping.
- Analysis of EHF gene expression in normal tissues and various carcinomas.
- Reporter assays to assess EHF protein's effect on stromelysin-1 and collagenase-1 promoter activity.
Main Results:
- The human EHF gene was localized to chromosome 11p12, a region frequently deleted in prostate, breast, and lung carcinomas.
- EHF exhibits differential expression in normal tissues and carcinomas, with higher expression in organs prone to cancer upon 11p12 deletion.
- EHF protein demonstrated repression of ETS-2-induced activity of stromelysin-1 and collagenase-1 promoters.
Conclusions:
- EHF is a candidate tumor suppressor gene located at the 11p12 locus.
- EHF's expression patterns and regulatory functions suggest a role in human development and carcinogenesis.
- Further research into EHF's function could elucidate its involvement in cancer development.