Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues.

Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues.
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DOI:
10.1186/1471-2407-10-9
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发表时间:
2010-01-11
期刊:
影响因子:
3.8
通讯作者:
Nardulli AM
Nardulli AM
中科院分区:
医学2区
文献类型:
--
作者:
Curtis CD;Thorngren DL;Nardulli AM

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在正常的细胞代谢过程中,氧被消耗并产生活性氧(ROS)。如果没有有效地消散,ROS可以积累并破坏常驻蛋白质,脂质和DNA。参与氧化还原调节和DNA修复的酶消散ROS并修复所产生的损伤,以保持功能性细胞环境。由于增加的ROS积累和/或未修复的DNA损伤可导致癌症的发生和进展,并且我们已经鉴定了许多影响MCF-7乳腺癌细胞雌激素反应性的氧化应激和DNA修复蛋白,这些蛋白质似乎可能在正常乳腺组织、良性增生(BH)、导管原位癌(DCIS)和浸润性乳腺癌(IBC)中差异表达。采用免疫组化方法检测60例乳腺组织中氧化应激蛋白、DNA修复蛋白和损伤标志物的表达。确定每个组织切片的相对平均强度,并使用方差分析来检测与正常乳腺组织相比BH、DCIS和IBC相对表达的统计差异。我们发现这些蛋白质中的一些在人乳腺癌组织中过表达,并且细胞定位发生了改变。我们的研究表明,氧化应激和DNA修复蛋白不仅保护正常细胞免受ROS的损伤作用,而且还可能促进乳腺肿瘤细胞的存活。
During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.
DOI: 10.1016/s0098-2997(00)00007-8
发表时间: 2000-12-01
影响因子: 10.6
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