C/EBPß Isoform Specific Gene Regulation: It's a Lot more Complicated than you Think!

It has been almost 30 years since C/EBPß was discovered. Seminal studies have shown that C/EBPß is a master regulator of mammary gland development and has been shown to control and influence proliferation and differentiation through varying mechanisms. The single-exon C/EBPß mRNA yields at least three different protein isoforms which have diverse, specific, context-dependent, and often non-overlapping roles throughout development and breast cancer progression. These roles are dictated by a number of complex factors including: expression levels of other C/EBP family members and their stoichiometry relative to the isoform in question, binding site affinity, post-translational modifications, co-factor expression, and even hormone levels and lactogenic status. Here we summarize the historical work up to the latest findings in the field on C/EBPß in the mammary gland and in breast cancer. With the current emphasis on improving immunotherapy in breast cancer the role of specific C/EBPß isoforms in regulating specific chemokine and cytokine expression and the immune microenvironment will be of increasing interest.