EXPRESSION OF THE TRANSFORMING GROWTH FACTOR-ALPHA EPIDERMAL GROWTH-FACTOR RECEPTOR PATHWAY IN NORMAL HUMAN-BREAST EPITHELIAL-CELLS
EXPRESSION OF THE TRANSFORMING GROWTH FACTOR-ALPHA EPIDERMAL GROWTH-FACTOR RECEPTOR PATHWAY IN NORMAL HUMAN-BREAST EPITHELIAL-CELLS
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DOI：
10.1210/endo-126-1-596
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发表时间：
1990-01-01
期刊：
影响因子：
4.8
通讯作者：
DICKSON, RB
中科院分区：
文献类型：
--
作者：
BATES, SE;VALVERIUS, EM;DICKSON, RB
为了更好地理解转化生长因子α-IFN-γ的可能作用和相互作用，（TGF α）及其受体，人乳腺上皮中的表皮生长因子（EGF）受体，我们研究了TGF α的表达。EGF受体在一系列正常人乳腺上皮细胞体外增殖前、体外短期增殖期和永生化后的表达。增加的TGF αmRNA表达与细胞在体外向增殖状态的转化相一致。在体外建立、繁殖和增殖后，细胞表达高水平的TGF α和TGF β。EGF受体mRNA加入不同的生长抑制剂，包括12-O-十四酰基佛波醇-13-乙酸酯（TPA），TGF β，和丁酸钠对这些快速增殖的细胞群之一（184号）的作用不能降低TGF α和β 1的表达。EGF受体同样，与184细胞的衰老和汇合相关的生长停止也不会导致表达减少。然而，TGF α. mRNA可以通过从培养基中撤出EGF或通过抗体介导的184细胞中EGF受体的阻断来证明。抗体介导的EGF受体阻断也导致生长和[3 H]胸苷标记的抑制。在增殖的乳腺上皮细胞中，一个自调节自分泌环似乎是起作用的。生长和TGF α的水平。mRNA的表达受EGF受体与配体结合的控制。这些研究表明TGF α/β 1的作用。表皮生长因子受体在正常乳腺细胞中的作用
To better understand the possible roles and interactions of transforming growth factor .alpha.- (TGF.alpha.) and its receptor, the epidermal growth factor (EGF) receptor in human breast epithelium, we have studied the expression of TGF.alpha. and the EGF receptor in a series of normal human mammary epithelial cells derived from reduction mammoplasty before in vitro propagation, during short term proliferation in vitro and after immortalization. Increased TGF.alpha. mRNA expression coincided with conversion of the cells to a proliferative state in vitro. After establishment, propagation, and proliferation in vitro, the cells expressed high levels of both TGF.alpha. and EGF receptor mRNAs. Addition of diverse growth inhibitory agents, including 12-O-tetradecanoylphorbol-13-acetate (TPA), TGF.beta., and sodium butyrate, to one of these rapidly proliferating cell populations (no. 184) failed to reduce the expression of either TGF.alpha. or the EGF receptor. Likewise, cessation of growth associated with both senescence and confluence of the 184 cells did not result in reduced expresssion. However, regulation of TGF.alpha. mRNA could be demonstrated by withdrawal of EGF from the medium or by antibody-mediated blockade of the EGF recetpor in 184 cells. Antibody-mediated EGF receptor blockade also results in inhibition of growth and [3H]thymidine labeling. An autoregulatory autocrine loop appears operant in proliferating breast epithelial cells. Both growth and levels of TGF.alpha. mRNA expression are controlled by binding of ligand to the EGF receptor. These studies suggest a role for the TGF.alpha./EGF receptor pathway in normal breast cell physiology.