Gigliotti A P, DeWille J W
The Ohio State University, Department of Veterinary Biosciences, Columbus 43210, USA.
Breast Cancer Res Treat. 1999 Nov;58(1):57-63. doi: 10.1023/a:1006381906288.
The repeated lactation cycles in the mammary gland offer a unique environment for the study of cell growth, differentiation, and death. The CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors important in growth control and differentiation in many tissues. Our laboratory and others have shown that C/EBP-delta and C/EBP-beta mRNA expression is closely associated with normal mouse mammary gland involution. To examine the relative influence of local versus systemic factors in C/EBP expression and tissue remodeling, a gland sealing mouse model was used. Mice with unilateral sealing continue to lactate and nurse pups via nonsealed glands, while sealed glands initiate involution. The expression of C/EBP-alpha, beta and delta mRNA was investigated in sealed and nonsealed nursing glands. In situ apoptosis was documented and glandular morphology was also examined. C/EBP-delta mRNA levels are low in nonsealed glands, but are rapidly and transiently induced in sealed glands by 24 h. C/EBP-beta mRNA expression is also relatively low in nonsealed glands, but is induced in sealed glands within 72 h. Expression of the apoptosis-associated mRNAs encoding bax and TRPM-2 is also induced in sealed glands by 24-48 h. Apoptosis and a moderate degree of tissue remodeling occur within the sealed glands in spite of systemic hormone levels capable of sustaining lactation. These data demonstrate that local factors are sufficient to induce C/EBP-beta and C/EBP-delta in the mouse mammary gland. In addition, mammary epithelial apoptosis and glandular remodeling occur in sealed glands, confirming a critical role for local factors in mammary involution.
乳腺中反复出现的泌乳周期为研究细胞生长、分化和死亡提供了独特的环境。CCAAT/增强子结合蛋白（C/EBPs）是一类转录因子，在许多组织的生长控制和分化中起重要作用。我们实验室和其他研究表明，C/EBP-δ和C/EBP-β mRNA表达与正常小鼠乳腺退化密切相关。为了研究局部因素与全身因素对C/EBP表达和组织重塑的相对影响，使用了一种腺体封闭小鼠模型。单侧封闭的小鼠通过未封闭的腺体继续泌乳并哺育幼崽，而封闭的腺体则开始退化。研究了封闭和未封闭的泌乳腺体中C/EBP-α、β和δ mRNA的表达。记录了原位凋亡情况，并检查了腺体形态。C/EBP-δ mRNA水平在未封闭的腺体中较低，但在封闭的腺体中24小时内迅速且短暂地诱导升高。C/EBP-β mRNA表达在未封闭的腺体中也相对较低，但在72小时内在封闭的腺体中被诱导。编码bax和TRPM-2的凋亡相关mRNA的表达在封闭的腺体中24至48小时内也被诱导。尽管全身激素水平能够维持泌乳，但封闭的腺体内仍发生凋亡和一定程度的组织重塑。这些数据表明，局部因素足以在小鼠乳腺中诱导C/EBP-β和C/EBP-δ。此外，封闭的腺体内发生乳腺上皮凋亡和腺体重塑，证实了局部因素在乳腺退化中的关键作用。
