Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
J Mammary Gland Biol Neoplasia. 2020 Mar;25(1):1-12. doi: 10.1007/s10911-020-09444-5. Epub 2020 Feb 20.
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.
自 C/EBPß 被发现以来，已经将近 30 年了。开创性的研究表明，C/EBPß 是乳腺发育的主要调节因子，通过不同的机制控制和影响增殖和分化。单外显子的 C/EBPß mRNA 至少产生三种不同的蛋白同工型，它们在发育和乳腺癌进展过程中具有不同的、特定的、上下文相关的、且通常不重叠的作用。这些作用由许多复杂因素决定，包括：其他 C/EBP 家族成员的表达水平及其与所讨论同工型的化学计量关系、结合位点亲和力、翻译后修饰、辅助因子表达，甚至激素水平和泌乳状态。在这里，我们总结了迄今为止在乳腺和乳腺癌领域关于 C/EBPß 的历史研究工作以及最新发现。随着当前对改善乳腺癌免疫疗法的重视，特定 C/EBPß 同工型在调节特定趋化因子和细胞因子表达以及免疫微环境中的作用将引起越来越多的兴趣。
