Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer.
Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer.
复制标题
乳腺癌的claudin-low内在亚型的表型和分子表征。
DOI：
10.1186/bcr2635
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Perou CM
中科院分区：
文献类型：
--
作者：
Prat A;Parker JS;Karginova O;Fan C;Livasy C;Herschkowitz JI;He X;Perou CM
在乳腺癌中，基因表达分析已经定义了五种肿瘤亚型（管腔A型、管腔B型、HER 2富集型、基底样型和封闭蛋白低型），每种亚型都具有独特的生物学和预后特征。在这里，我们全面描述了最近发现的低密蛋白肿瘤亚型。使用更新的人类肿瘤数据库和多个独立的数据集，将低密蛋白肿瘤的临床、病理和生物学特征与其他肿瘤亚型进行比较。还在一组乳腺癌细胞系和基因工程小鼠模型中评估了claudin低肿瘤的这些主要特征。紧密连接蛋白-低肿瘤的特征在于管腔分化标志物的低表达或不表达，上皮-间充质转化标志物、免疫应答基因和癌症干细胞样特征的高度富集。临床上，大多数低密蛋白肿瘤是预后不良的雌激素受体（ER）阴性、孕激素受体（PR）阴性和表皮生长因子受体2（HER 2）阴性（三阴性）浸润性导管癌，具有高发生率的化生和髓样分化。它们对标准术前化疗的反应率也介于基底样肿瘤和管腔肿瘤之间。有趣的是，我们发现一组高度利用的乳腺癌细胞系和几种基因工程小鼠模型表达了低密蛋白表型。最后，我们证实，在所有的乳腺癌中存在一个与乳腺上皮干细胞最相似的低密蛋白亚型，这是一个病理相关的分化层次。这些结果有助于提高我们对乳腺癌生物学异质性的理解，并为进一步评估claudin低肿瘤和细胞系的独特生物学提供工具。
In breast cancer, gene expression analyses have defined five tumor subtypes (luminal A, luminal B, HER2-enriched, basal-like and claudin-low), each of which has unique biologic and prognostic features. Here, we comprehensively characterize the recently identified claudin-low tumor subtype. The clinical, pathological and biological features of claudin-low tumors were compared to the other tumor subtypes using an updated human tumor database and multiple independent data sets. These main features of claudin-low tumors were also evaluated in a panel of breast cancer cell lines and genetically engineered mouse models. Claudin-low tumors are characterized by the low to absent expression of luminal differentiation markers, high enrichment for epithelial-to-mesenchymal transition markers, immune response genes and cancer stem cell-like features. Clinically, the majority of claudin-low tumors are poor prognosis estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and epidermal growth factor receptor 2 (HER2)-negative (triple negative) invasive ductal carcinomas with a high frequency of metaplastic and medullary differentiation. They also have a response rate to standard preoperative chemotherapy that is intermediate between that of basal-like and luminal tumors. Interestingly, we show that a group of highly utilized breast cancer cell lines, and several genetically engineered mouse models, express the claudin-low phenotype. Finally, we confirm that a prognostically relevant differentiation hierarchy exists across all breast cancers in which the claudin-low subtype most closely resembles the mammary epithelial stem cell. These results should help to improve our understanding of the biologic heterogeneity of breast cancer and provide tools for the further evaluation of the unique biology of claudin-low tumors and cell lines.
登录
查看更多内容
影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
10.3
作者：
Lakhani, SR;Jacquemier, J;Easton, DF
通讯作者：
Easton, DF