Darcy K M, Zangani D, Wohlhueter A L, Huang R Y, Vaughan M M, Russell J A, Ip M M
Department of Pharmacology and Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
J Histochem Cytochem. 2000 Jan;48(1):63-80. doi: 10.1177/002215540004800107.
Studies were undertaken to examine the natural role of ErbB2, ErbB3, and ErbB4 during the development of normal rat mammary epithelial cells (MECs) in vivo and in vitro. Immunohistochemical analysis demonstrated that mammary gland terminal end buds expressed abundant ErbB2 and ErbB4 but limited ErbB3 in pubescent rats, whereas luminal epithelial cells in nulliparous rats expressed ErbB2, ErbB3, and/or ErbB4. During pregnancy, ductal epithelial cells and stromal cells expressed abundant ErbB3 but limited ErbB2. Although ErbB2 and ErbB3 were downregulated throughout lactation, both receptors were re-expressed during involution. In contrast, ErbB4 was downregulated throughout pregnancy, lactation, and involution. Immunoblotting and immunoprecipitation studies confirmed the developmental expression of ErbB2 and ErbB3 in the mammary gland and the co-localization of distinct ErbB receptors in the mammary gland of nulliparous rats. In agreement with our in vivo findings, primary culture studies demonstrated that ErbB2 and ErbB3 were expressed in functionally immature, terminally differentiated and apoptotic MECs, and downregulated in functionally differentiated MECs. ErbB receptor signaling was required for epithelial cell growth, functional differentiation, and morphogenesis of immature MECs, and the survival of terminally differentiated MECs. Finally, ErbB4 expression did not interfere with functional differentiation and apoptosis of normal MECs.
开展了多项研究，以考察ErbB2、ErbB3和ErbB4在正常大鼠乳腺上皮细胞（MECs）体内和体外发育过程中的天然作用。免疫组织化学分析表明，青春期大鼠的乳腺终末芽表达丰富的ErbB2和ErbB4，但ErbB3表达有限，而未生育大鼠的管腔上皮细胞表达ErbB2、ErbB3和/或ErbB4。在怀孕期间，导管上皮细胞和基质细胞表达丰富的ErbB3，但ErbB2表达有限。尽管ErbB2和ErbB3在整个哺乳期均下调，但在退化期均重新表达。相比之下，ErbB4在整个怀孕期、哺乳期和退化期均下调。免疫印迹和免疫沉淀研究证实了ErbB2和ErbB3在乳腺中的发育表达以及未生育大鼠乳腺中不同ErbB受体的共定位。与我们的体内研究结果一致，原代培养研究表明，ErbB2和ErbB3在功能不成熟、终末分化和凋亡的MECs中表达，并在功能分化的MECs中下调。ErbB受体信号传导是未成熟MECs上皮细胞生长、功能分化和形态发生以及终末分化MECs存活所必需的。最后，ErbB4的表达不影响正常MECs的功能分化和凋亡。
