Darcy K M, Wohlhueter A L, Zangani D, Vaughan M M, Russell J A, Masso-Welch P A, Varela L M, Shoemaker S F, Horn E, Lee P P, Huang R Y, Ip M M
Department of Pharmacology and Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Eur J Cell Biol. 1999 Jul;78(7):511-23. doi: 10.1016/S0171-9335(99)80077-6.
Epidermal growth factor (EGF) is a multifunctional regulator of mammary epithelial cells (MEC) that transduces its signals through the EGF receptor (EGFR). To clarify the role of the EGFR in the mammary gland, EGFR expression, localization and function were examined during different developmental stages in rats. Immunoblot analysis demonstrated high levels of EGFR during puberty, pregnancy and involution as well as at sexual maturity, and low levels throughout lactation. An immunohistochemical assay was used to show that EGFR was distinctly expressed in a variety of cell types throughout mammary glands from virgin rats and rats during pregnancy and involution, and was down-regulated in all cell types throughout lactation. To examine the relationship between EGFR expression and function, primary MEC were cultured under conditions that induced physiologically relevant growth, morphogenesis and lactogenesis. Cultured MEC expressed an in vivo-like profile of EGFR. EGFR was high in immature MEC, down-regulated in functionally differentiated MEC, and then up-regulated in terminally differentiated and apoptotic MEC. An inhibitor of the tyrosine kinase domain of EGFR was used to demonstrate that EGFR signaling was required for growth and differentiation of immature MEC, and for survival of terminally differentiated MEC, but not for maintaining functional differentiation.
表皮生长因子（EGF）是乳腺上皮细胞（MEC）的多功能调节因子，它通过表皮生长因子受体（EGFR）转导信号。为阐明EGFR在乳腺中的作用，研究了大鼠不同发育阶段的EGFR表达、定位和功能。免疫印迹分析表明，青春期、妊娠期、退化期以及性成熟时EGFR水平较高，而整个哺乳期水平较低。免疫组织化学分析显示，从处女鼠、妊娠和退化期大鼠的整个乳腺中，EGFR在多种细胞类型中均有明显表达，而在整个哺乳期所有细胞类型中均下调。为研究EGFR表达与功能之间的关系，在诱导生理相关生长、形态发生和泌乳的条件下培养原代MEC。培养的MEC表达出与体内相似的EGFR表达模式。EGFR在未成熟MEC中水平较高，在功能分化的MEC中下调，然后在终末分化和凋亡的MEC中上调。使用EGFR酪氨酸激酶结构域抑制剂证明，EGFR信号传导对于未成熟MEC的生长和分化以及终末分化MEC的存活是必需的，但对于维持功能分化并非必需。
