The epithelial-specific Ets factors occupy a unique position in defining epithelial proliferation, differentiation and carcinogenesis

Abstract

The Ets family of transcription factors regulates many biological processes. Within the Ets family are a subset of proteins that have epithelial restricted expression patterns, both in tissues and cell lines. These Epithelial-specific Ets (Ese) factors, cluster into two groups based on the sequence of the Ets DNA binding domain: (i) Ese1, Ese2 and Ese3, and (ii) the more divergent, Pdef. Gene targeting and cell culture studies have demonstrated that Ese factors are important for cellular differentiation. Furthermore, the ability of Ese factors to regulate expression of genes that are markers of differentiation supports this model. Significantly, the expression profile of these Ese factors is altered in epithelial cancers relative to the respective normal tissues. It is likely that this variation in expression affects downstream target genes important for carcinogenesis such as oncogenes and tumor suppressor genes. Understanding the role of these Ese factors in normal cellular differentiation may elucidate specific mechanisms by which cancer cells can become undifferentiated.