ETS factors are known to act as positive or negative regulators of the expression of genes including those that
control response to various signaling cascades, cellular proliferation, differentiation, hematopoiesis, apoptosis, adhesion,
migration, invasion and metastasis, tissue remodeling, ECM composition and angiogenesis. During cancer progression,
altered ETS gene expression disrupts the regulated control of many of these biological processes. Although it was
originally observed that specific ETS factors function either as positive or negative regulators of transcription, it is now
evident that the same ETS factor may function in reciprocal fashions, reflecting promoter and cell context specificities.
This report will present a discussion of ETS factor expression during prostate and breast cancer progression and its
functional roles in epithelial cell phenotypes.
The ETS genes encode transcription factors that have independent activities but are likely to be part of an integrated
network. While previous studies have focused on single ETS factors in the context of specific promoters, future studies
should consider the functional impact of multiple ETS present within a specific cell type. The pattern of ETS expression
within a single tissue is, not surprisingly, quite complex. Multiple ETS factors may be able to regulate the same genes,
albeit at different magnitude or in different directions. Furthermore, the precise balance between cancer promotion and
inhibition by ETS factors, which may differentially regulate specific target genes, can thus control its progression. These
concepts form the basis of the hypothesis that "Ets conversion" plays a critical role during tumor progression. Examples
supporting this hypothesis will be described.