Davies Claire R, Morris Joanna S, Griffiths Matthew R, Page Martin J, Pitt Andrew, Stein Torsten, Gusterson Barry A
Department of Pathology, Division of Cancer Sciences and Molecular Pathology, Glasgow, Scotland, UK.
Proteomics. 2006 Nov;6(21):5694-704. doi: 10.1002/pmic.200600202.
After lactation, the mouse mammary gland undergoes apoptosis and tissue remodelling as the gland reverts to its prepregnant state. This complex change was investigated using 2-DE. An integrated database was produced from lactation and involution proteomes. Forty-four molecular cluster indexes (MCIs) that showed altered expression from lactation to involution were selected for MS analysis. Of these, 32 gave protein annotations, 18 of which were unequivocal proteins. Selected proteins were then studied across all of development, including pregnancy, using data integrated from another proteome database. Two proteins, the RNA polymerase B transcription factor 3 (BTF3) and the minichromosome maintenance protein 3 (MCM3), although initially selected on the basis of the lactation/involution criteria, had expression profiles that indicated an additional role in mammary development and were further analysed. BTF3, a transcription factor previously not described in the mammary gland, was up-regulated strongly in pregnancy, indicating an involvement in alveolar growth. MCM3's expression was greatest in pregnancy and late involution, decreasing through lactation. Immunohistochemistry localised MCM3 to the mammary epithelium, where a greater proportion of cells stained than for the proliferation marker Ki67. MCM3 expression during lactation may identify cells that are licensed to repopulate the gland during cell loss in lactation and following involution.
哺乳期结束后，小鼠乳腺会经历细胞凋亡和组织重塑，腺体恢复到妊娠前状态。利用双向电泳对这一复杂变化进行了研究。从泌乳和退化蛋白质组构建了一个综合数据库。选择了44个从泌乳到退化表达发生改变的分子聚类指标（MCI）进行质谱分析。其中，32个给出了蛋白质注释，其中18个是明确的蛋白质。然后，利用从另一个蛋白质组数据库整合的数据，对所有发育阶段（包括妊娠）的选定蛋白质进行研究。两种蛋白质，RNA聚合酶B转录因子3（BTF3）和微小染色体维持蛋白3（MCM3），尽管最初是根据泌乳/退化标准选择的，但它们的表达谱表明在乳腺发育中还有额外作用，因此进行了进一步分析。BTF3是一种先前未在乳腺中描述过的转录因子，在妊娠期间强烈上调，表明其参与肺泡生长。MCM3的表达在妊娠和退化后期最高，在泌乳期降低。免疫组织化学将MCM3定位到乳腺上皮，其中染色的细胞比例高于增殖标记物Ki67。泌乳期间MCM3的表达可能识别出在泌乳期细胞丢失和退化后能够重新填充腺体的细胞。
