Hyperplasia, reduced E-cadherin expression, and developmental arrest in mammary glands oxidatively stressed by loss of mitochondrial superoxide dismutase
Hyperplasia, reduced E-cadherin expression, and developmental arrest in mammary glands oxidatively stressed by loss of mitochondrial superoxide dismutase
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DOI：
10.1016/j.breast.2005.02.004
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发表时间：
2005-08-01
期刊：
影响因子：
3.9
通讯作者：
Benz, CC
中科院分区：
文献类型：
--
作者：
Parmar, H;Melov, S;Benz, CC
为了研究过度氧化应激对乳腺发育的失调作用，从具有正常（+/+）或缺乏（null，-/-）锰超氧化物歧化酶（SOD 2）的新生雌性小鼠中切除乳腺原基，并将其植入正常宿主雌性裸鼠的肾包膜下，同时补充/不补充雌激素。30天后，切除移植的腺体进行整体计数、显微镜和免疫组织化学评价。与移植的SOD 2 +/+腺体的正常生长和成熟相反，SOD 2-/-腺体表现出发育停滞、导管生长和分支减少以及管腔缺失。这些亚形态SOD 2-/-导管含有增生上皮，Ki-67标记增加，E-钙粘蛋白表达丢失，表达基底和肌上皮成分的p63和细胞角蛋白（K）-14表达紊乱。雌激素治疗未能上调孕激素受体或正常化的发展。这些研究结果表明，SOD 2功能丧失导致的过度氧化应激可阻止乳腺成熟并诱导具有早期癌前特征的增生上皮。(c)2005爱思唯尔有限公司保留所有权利。
To investigate the dysregulating effect of excess oxidative stress on mammary gland development, mammary anlage from newborn female mice with normal (+/+) or absent (null, -/-) manganese superoxide dismutase (SOD2) were excised and implanted under the renal capsule of normal host female nude mice with/without concurrent estrogen supplementation. After 30 days the transplanted glands were excised for wholemount, microscopic and immunohistochemical evaluation. In contrast to the normal growth and maturation of transplanted SOD2+/+ glands, SOD2-/- glands showed arrested development, reduced ductal outgrowth and branching, and absent lumen. These hypomorphic SOD2-/- ducts contained hyperplastic epithelium with increased Ki-67 labelling, toss of E-cadherin expression, and disorganized p63 and cytokeratin (K)-14 expressing basal and myoepithetial components. Estrogen treatment failed to upregulate progesterone receptor or normalize development. These findings suggest that excess oxidative stress from loss of SOD2 function can arrest mammary gland maturation and induce hyperplastic epithelium with early premalignant features. (c) 2005 Elsevier Ltd. All rights reserved.