Altered intracellular region of MUC1 and disrupted correlation of polarity-related molecules in breast cancer subtypes.

Altered intracellular region of MUC1 and disrupted correlation of polarity-related molecules in breast cancer subtypes.
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DOI:
10.1111/cas.12596
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发表时间:
2015-03
期刊:
影响因子:
5.7
通讯作者:
Masuda S
Masuda S
中科院分区:
医学2区
文献类型:
--
作者:
Iizuka M;Nakanishi Y;Fuchinoue F;Maeda T;Murakami E;Obana Y;Enomoto K;Tani M;Sakurai K;Amano S;Masuda S

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MUC 1糖蛋白在乳腺癌肿瘤发生期间过表达且其细胞内定位发生改变。本研究旨在阐明MUC 1的胞浆定位与乳腺癌亚型的关系以及与乳腺癌亚型中细胞极性相关的10种分子的相关性。我们免疫染色131福尔马林固定和石蜡包埋的乳腺癌标本与抗MUC 1抗体(MUC 1/CORE)。对于131例肿瘤标本中的48例,进行激光辅助显微切割和实时定量RT-PCR以分析MUC 1和10种分子β-catenin、E-cadherin、claudin 3、claudin 4、claudin 7、RhoA、cdc 42、Rac 1、Par 3和Par 6的mRNA水平。MUC 1蛋白在不同亚型乳腺癌中的定位不同,管腔型A样肿瘤中MUC 1蛋白在顶区和胞浆均有表达(P < 0.01),管腔型B样(生长因子受体2 [HER 2]+)肿瘤中MUC 1蛋白在胞浆和细胞膜均有表达(P < 0.05),三阴性肿瘤中MUC 1蛋白无表达(P < 0.001)。雌激素受体(ER)阳性乳腺癌的MUC 1 mRNA水平高于ER阴性乳腺癌(P < 0.01)。10种分子中的两种(55种组合)之间表达水平的相互相关性的发生率在正常乳腺组织中为54.5%,在管腔A样标本中为38.2%,在管腔B样(HER 2+)中为16.4%,在HER 2中为3.6%,在三阴性标本中为18.2%。总之,每种乳腺癌亚型具有MUC 1的特征性细胞质定位模式,并且与正常乳腺组织相比,10种检查分子之间的表达水平具有不同程度的破坏相关性。
MUC1 glycoprotein is overexpressed and its intracellular localization altered during breast carcinoma tumorigenesis. The present study aimed to clarify the relationship of cytoplasmic localization of MUC1 with the breast cancer subtype and the correlation of 10 molecules associated with cell polarity in breast cancer subtypes. We immunostained 131 formalin-fixed and paraffin-embedded breast cancer specimens with an anti-MUC1 antibody (MUC1/CORE). For 48 of the 131 tumor specimens, laser-assisted microdissection and real-time quantitative RT-PCR were performed to analyze mRNA levels of MUC1 and 10 molecules, β-catenin, E-cadherin, claudin 3, claudin 4, claudin 7, RhoA, cdc42, Rac1, Par3 and Par6. Localization of MUC1 protein varied among breast cancer subtypes, that is, both the apical domain and cytoplasm in luminal A-like tumors (P < 0.01) and both the cytoplasm and cell membrane in luminal B-like (growth factor receptor 2 [HER2]+) tumors (P < 0.05), and no expression was found in triple negative tumors (P < 0.001). Estrogen receptor (ER)+ breast cancers showed higher MUC1 mRNA levels than ER− breast cancers (P < 0.01). The incidence of mutual correlations of expression levels between two of the 10 molecules (55 combinations) was 54.5% in normal breast tissue and 38.2% in luminal A-like specimens, 16.4% in luminal B-like (HER2+), 3.6% in HER2 and 18.2% in triple negative specimens. In conclusion, each breast cancer subtype has characteristic cytoplasmic localization patterns of MUC1 and different degrees of disrupted correlation of the expression levels between the 10 examined molecules in comparison with normal breast tissue.
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