INHIBITION OF MOUSE MAMMARY DUCTAL MORPHOGENESIS AND DOWN-REGULATION OF THE EGF RECEPTOR BY EPIDERMAL GROWTH-FACTOR
INHIBITION OF MOUSE MAMMARY DUCTAL MORPHOGENESIS AND DOWN-REGULATION OF THE EGF RECEPTOR BY EPIDERMAL GROWTH-FACTOR
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DOI：
10.1016/0012-1606(90)90267-m
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发表时间：
1990-02-01
影响因子：
2.7
通讯作者：
DANIEL, CW
中科院分区：
文献类型：
--
作者：
COLEMAN, S;DANIEL, CW
EGF最初被证明是多种细胞类型的有效有丝分裂原，最近已被证明可以抑制几种细胞系的增殖。然而，很少有研究涉及EGF对体内组织生长和形态发生的影响，特别是关于EGF作为一种可能的抑制剂。我们现在证明，EGF治疗蓬勃发展的乳腺导管，直接给药的腺体缓慢释放塑料植入物，抑制正常的导管生长。抑制仅限于植入物周围的区域，同一动物中未处理的腺体是正常的，表明EGF的直接作用。EGF处理的端芽较小，并表现出降低水平的DNA合成，虽然残余的干（帽）细胞层持续存在。生长的完全抑制发生在植入后3天内，需要延长暴露于EGF，因为5小时或更少的治疗对导管生长没有影响。在测试的较低抑制剂量下，生长在8天内恢复，表明抑制可逆。未见小叶肺泡或增生反应。125 I-EGF放射自显影显示，导管生长抑制之前的EGF受体位于端芽上皮的帽细胞层和邻近芽的基质细胞的消失。这些结果，结合我们以前的证据表明，生长刺激作用的EGF对非增殖乳腺导管，表明生长调节作用的EGF在小鼠乳腺导管形态发生。
EGF, initially demonstrated to be a potent mitogen for a variety of cell types, has more recently been shown to inhibit proliferation of several cell lines. Few studies, however, have addressed the effects of EGF on growth and morphogenesis of tissues in vivo, particularly with regard to EGF as a possible inhibitor. We now demonstrate that EGF treatment of vigorously growing mammary ducts, administered directly to the glands by slow release plastic implants, inhibited normal ductal growth. Inhibition was restricted to the region around the implant and untreated glands in the same animal were normal, indicating direct effects of EGF. EGF-treated end buds were smaller and demonstrated reduced levels of DNA synthesis, although remnants of a stem (cap) cell layer persisted. Full inhibition of growth occurred within 3 days of implantation and required extended exposure to EGF, since treatment of 5 hr or less had no effect on ductal growth. At the lower inhibitory doses tested, growth resumed within 8 days, indicating reversibility of inhibition. No lobuloalveolar or hyperplastic response was seen. 125I-EGF autoradiography revealed that ductal growth inhibition was preceded by the disappearance of EGF receptors located in the cap cell layer of the end bud epithelium and in stromal cells adjacent to the buds. These results, in conjunction with our previous evidence demonstrating the growth-stimulatory effect of EGF on nonproliferating mammary ducts, suggest a growth regulatory role for EGF in mouse mammary ductal morphogenesis.