Alteration in protein expression in estrogen receptor alpha-negative human breast cancer tissues indicates a malignant and metastatic phenotype.

Alteration in protein expression in estrogen receptor alpha-negative human breast cancer tissues indicates a malignant and metastatic phenotype.
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DOI:
10.1007/s10585-010-9338-8
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发表时间:
2010-10
影响因子:
4
通讯作者:
Sang, Qing-Xiang Amy
Sang, Qing-Xiang Amy
中科院分区:
医学3区
文献类型:
--
作者:
Sahab, Ziad J.;Man, Yan-Gao;Semaan, Suzan M.;Newcomer, Robert G.;Byers, Stephen W.;Sang, Qing-Xiang Amy

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导管原位癌是最早可识别的乳腺癌病变。肌上皮细胞层和基底膜的破坏是DCIS开始侵入基质的先决条件。覆盖在局部破坏的肌上皮细胞层上的大多数上皮细胞是雌激素受体α阴性或ER(-);然而,由完整的肌上皮细胞层限定的同一导管内的相邻细胞表达高水平的ER。这些ER(+)和ER(-)细胞是从乳腺癌患者的相同导管中显微解剖的。ER(+)和ER(-)细胞表达的差异蛋白用双向凝胶电泳、质谱和Western印迹分析鉴定。ER(-)细胞表达较低水平的超氧化物歧化酶、Ral A蛋白、半乳糖凝集素-1、尿苷磷酸化酶、细胞视黄酸结合蛋白1、S100钙结合蛋白A11和核苷二磷酸激酶A或非转移蛋白23-H1(nm 23-H1)。上调的蛋白质Rho GDP-解离抑制剂1 α可能诱导化疗耐药性。重要的发现是,显微切割的ER(-)细胞表达的细胞视黄酸结合蛋白1(一种参与细胞分化的蛋白质)和核苷二磷酸激酶A(nm 23-H1)(一种转移抑制因子)比相邻的ER(+)细胞少13.5倍,表达的蛋白质也少34.2倍。ER(-)细胞中蛋白表达改变的共同作用可能是促进比邻近ER(+)细胞更恶性的表型,包括经历凋亡和分化的能力降低,以及DNA损伤、转移和抵抗化疗的可能性增加。
Ductal carcinoma in situ represents an earliest identifiable breast cancer lesion. The disruption of the myoepithelial cell layer and basement membrane is a prerequisite for DCIS to initiate invasion into the stroma. The majority of epithelial cells overlying a focally disrupted myoepithelial cell layer are estrogen receptor-alpha negative, or ER(-); however, adjacent cells within the same duct confined by an intact myoepithelial cell layer express high levels of ER. These ER (+) and ER (-) cells were microdissected from the same ducts of breast cancer patients. Differential proteins expressed by ER(+) and ER(-) cells were identified using two-dimensional gel electrophoresis followed by mass spectrometry and Western blot analysis. ER(-) cells express lower levels of superoxide dismutase, Ral A protein, galectin-1, uridine phosphorylase, cellular retinoic acid-binding protein 1, S100 calcium binding protein A11, and nucleoside diphosphate kinase A or non-metastasis protein 23-H1 (nm23-H1). The upregulated protein, Rho GDP-Dissociation Inhibitor 1 alpha, may induce chemotherapy resistance. The significant findings are that the microdissected ER(-) cells express 13.5 times less cellular retinoic acid-binding protein 1, a protein involved in cellular differentiation, and 34.2 times less nucleoside diphosphate kinase A or (nm23-H1), a metastasis suppressor, and express fewer proteins than adjacent ER(+) cells. The collective role of the alteration of protein expression in ER(-) cells may be promoting a more malignant phenotype than adjacent ER(+) cells, including decreased ability to undergo apoptosis and differentiation, and increased potential to damage DNA, metastasize, and resist chemotherapy.
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发表时间: 2000-08-08
期刊: BIOCHEMISTRY
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DOI: 10.1038/320134a0
发表时间: 1986-03-13
期刊: NATURE
影响因子: 64.8
作者:
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通讯作者: CHAMBON, P