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.
Subject(s)
Chromosomes, Human, Pair 11 , Gene Expression Regulation, Neoplastic , Neoplasms/metabolism , Transcription Factors/genetics , Amino Acid Sequence , Base Sequence , Chromosome Mapping , DNA, Complementary/analysis , Humans , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 3/metabolism , Molecular Sequence Data , Promoter Regions, Genetic/physiology , Tissue Distribution , Transcription Factors/biosynthesis , Transcription Factors/physiologyABSTRACT
The ets family is a large multigene family of transcription factors that share a conserved DNA-binding "ETS" domain and include several oncoproteins that induce tumorigenesis when overexpressed. Here we report the cDNA cloning from mouse pituitary somatotroph tumors, sequence characterization and tissue-specific expression pattern in mice of a novel ets family gene, "Ehf" ("ets homologous factor"). The putative 300 amino acid Ehf protein is a highly divergent ets family member, but is most related to the recently identified oncoprotein ESX (36% overall and 84% ETS domain amino acid identity). Thus, Ehf and ESX comprise a new ets subfamily. Ehf is a single-copy gene, but produces four distinct mRNA transcripts. Ehf transcripts are abundant in mouse kidney and lung, less so in muscle and liver, and not detected in brain, spleen or testes. Because of its presence in somatotroph tumors and its relationship to ESX, Ehf may represent a new oncoprotein.
