Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada.
PLoS One. 2011;6(11):e27795. doi: 10.1371/journal.pone.0027795. Epub 2011 Nov 16.
Adipocyte enhancer binding protein 1 (AEBP1) is a multifunctional protein that negatively regulates the tumor suppressor PTEN and IκBα, the inhibitor of NF-κB, through protein-protein interaction, thereby promoting cell survival and inflammation. Mice homozygous for a disrupted AEBP1 gene developed to term but showed defects in growth after birth. AEBP1(-/-) females display lactation defect, which results in the death of 100% of the litters nursed by AEBP1(-/-) dams. Mammary gland development during pregnancy appears normal in AEBP1(-/-) dams; however these mice exhibit expansion of the luminal space and the appearance of large cytoplasmic lipid droplets (CLDs) in the mammary epithelial cells at late pregnancy and parturition, which is a clear sign of failed secretory activation, and accumulation of milk proteins in the mammary gland, presumably reflecting milk stasis following failed secretory activation. Eventually, AEBP1(-/-) mammary gland rapidly undergoes involution at postpartum. Stromal restoration of AEBP1 expression by transplanting wild-type bone marrow (BM) cells is sufficient to rescue the mammary gland defect. Our studies suggest that AEBP1 is critical in the maintenance of normal tissue architecture and function of the mammary gland tissue and controls stromal-epithelial crosstalk in mammary gland development.
脂肪细胞增强结合蛋白 1（AEBP1）是一种多功能蛋白，通过蛋白-蛋白相互作用，负调控肿瘤抑制因子 PTEN 和 NF-κB 的抑制剂 IκBα，从而促进细胞存活和炎症。基因敲除 AEBP1 的杂合子小鼠能够正常发育至足月，但出生后生长出现缺陷。AEBP1(-/-)雌性小鼠表现出泌乳缺陷，这导致由 AEBP1(-/-)母鼠哺乳的所有幼崽全部死亡。AEBP1(-/-)孕鼠的乳腺在怀孕期间发育正常；然而，这些小鼠在妊娠晚期和分娩时表现出腔隙扩张和乳腺上皮细胞中出现大的细胞质脂滴（CLD），这是分泌激活失败的明显迹象，以及乳腺中乳蛋白的积累，可能反映了分泌激活失败后的乳汁淤积。最终，AEBP1(-/-)乳腺在产后迅速经历退化。通过移植野生型骨髓（BM）细胞来恢复 AEBP1 的表达足以挽救乳腺缺陷。我们的研究表明，AEBP1 对于维持乳腺组织的正常组织结构和功能以及控制乳腺发育中的基质-上皮细胞相互作用至关重要。
