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

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

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.

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Acknowledgements

These studies were supported by grant CA16303 from the National Cancer Institute. We would like to thank Dr. Sandy Grimm for generously providing us with the figure illustrating C/EBPß expression in the mammary gland throughout development. While we tried to be as comprehensive as possible, we apologize to those investigators whose work we were unable to cite due to space limitations.

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  1. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    Aaron J. Spike & Jeffrey M. Rosen

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Spike, A.J., Rosen, J.M. C/EBPß Isoform Specific Gene Regulation: It’s a Lot more Complicated than you Think!. J Mammary Gland Biol Neoplasia 25, 1–12 (2020). https://doi.org/10.1007/s10911-020-09444-5

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